George R. Stark

DNA synthesis from unbalanced nucleotide pools causes limited DNA damage that triggers ATR-CHK1-dependent p53 activation. (2008)

Hastak, Kedar, Paul, Rajib K., Agarwal, Mukesh K., Thakur, Vijay S., Agrawal, Sudesh, ...

p53-dependent G(1) and G(2) cell cycle checkpoints are activated in response DNA damage that help to maintain genomic stability. p53 also helps to protect cells from damage that occurs during S...

Unphosphorylated STAT3 accumulates in response to IL-6 and activates transcription by binding to NF{kappa}B (2007)

Yang, Jinbo, Liao, Xudong, Agarwal, Mukesh K., Barnes, Laura, Auron, Philip E., Stark, George R.

gp130-linked cytokines such as interleukin-6 (IL-6) stimulate the formation of tyrosine-phosphorylated signal transducer and activator of transcription 3 (P-STAT3), which activates many genes,...

Macrophage inhibitory cytokine 1 mediates a p53-dependent protective arrest in S phase in response to starvation for DNA precursors. (2006)

Agarwal, Mukesh K., Hastak, Kedar, Jackson, Mark W., Breit, Samuel N., Stark, George R., Agarwal, Munna L.

p53 is essential for the cellular responses to DNA damage that help to maintain genomic stability. Protective p53-dependent cell-cycle checkpoints are activated in response to a wide variety of...

Summary (2005)

Mark W. Jackson, Mukesh K. Agarwal, Jinbo Yang, Patrick Bruss, Takeshi Uchiumi, Munna L. Agarwal, ...

p130/p107/p105Rb-dependent transcriptional repression during DNA-damage-induced cell-cycle

Forward genetics in mammaliancells: functional approaches to gene discovery (1999)

Stark, George R., Gudkov, AndreiV.

Definitive proof of function in biological systemsrequires genetic analysis. Only when the loss of a particular proteincorresponds to the loss of a specific function can one be sure thatthe protein...

Inhibition of the cellular response to interferons by products of the adenovirus type 5 E1A oncogene (1991)

Ackrill, Andrew M., Foster, Graham R., Laxton, Carl D., Flavell, David M., Stark, George R., Kerr, Ian M.

Expression of the E1A oncogene of adenovirus type 5 inhibits the response of interferon (IFN)-inducible constructs to Type I (α,β) and II (γ) IFNs in transient transfection assays. In human cell...

Differential response of the human 6-16 and 9-27 genes to {alpha} and {gamma} interferons (1991)

Ackrill, Andrew M., Reid, Laurence E., Gilbert, Christopher S., Gewert, Dirk R., Porter, Andrew C.G., Lewin, Andrew R., ...

9–27 mRNA is expressed to a high level in response to both α and γ interferons. In contrast, 6–16 mRNA Is expressed well in response to α but very poorly in response to γ interferon in human...

High frequency of double resistance in the B16 melanoma cell line. (1990)

McMillan, Trevor J., Kalebic, Tia, Stark, George R., Hart, Ian R.

Methotrexate (MTX) and N-(phosphonacetyl)- -aspartate (PALA) are two agents to which cellular resistance can be conferred by gene amplification, but they do not generally show cross resistance....

Transcription factors induced by interferons {alpha} and {gamma} (1990)

Imam, A.M.Ali, Ackrill, Andrew M., Dale, Trevor C., Kerr, Ian M., Stark, George R.

Factors induced by interferons (IFNs) bind to the IFN-stimulated response elements (ISREs) of many genes. In human cells treated with type I ( α, β) IFN, factor E is induced in about 1 min and...

Quantitative analysis of specific labelled RNA's using DNA covalently linked to diazobenzyloxy-methyl-paper (1979)

Stark, George R.

Substantial amounts of DNA (at least 25 µg per cm 2) can be stably bound to diazobenzyloxymethyl(DBM)-paper Complementary RNA will hybridize to the DNA paper almost completely in 24 hours.Using...

Mechanisms of sod2 Gene Amplification in Schizosaccharomyces pombe

Albrecht, Elizabeth B., Hunyady, Aaron B., Stark, George R., Patterson, Thomas E.

Gene amplification in eukaryotes plays an important role in drug resistance, tumorigenesis, and evolution. The Schizosaccharomyces pombe sod2 gene provides a useful model system to analyze this...

Stabilization and activation of p53 are regulated independently by different phosphorylation events

Chernov, Mikhail V., Ramana, Chilakamarti V., Adler, Victor V., Stark, George R.

Treatment of mouse or human cells with the protein kinase C (PKC) inhibitors H7 or bisindolylmaleimide I induced an increase in the lifetime of p53, leading to its accumulation. In inhibitor-treated...

A mutant cell line defective in response to double-stranded RNA and in regulating basal expression of interferon-stimulated genes

Leaman, Douglas W., Salvekar, Anupama, Patel, Rekha, Sen, Ganes C., Stark, George R.

Although much progress has been made in identifying the signaling pathways that mediate the initial responses to interferons (IFNs), much less is known about how IFN-stimulated genes (ISGs) are kept...

Receptor-associated constitutive protein tyrosine phosphatase activity controls the kinase function of JAK1

Haque, S. Jaharul, Wu, Qian, Kammer, Winfried, Friedrich, Karlheinz, Smith, Jonathan M., Kerr, Ian M., ...

Exposure of cells to protein tyrosine phosphatase (PTP) inhibitors causes an increase in the phosphotyrosine content of many cellular proteins. However, the level at which the primary signaling event...

A p53-dependent S-phase checkpoint helps to protect cells from DNA damage in response to starvation for pyrimidine nucleotides

Agarwal, Munna L., Agarwal, Archana, Taylor, William R., Chernova, Olga, Sharma, Yogesh, Stark, George R.

Normal mammalian cells arrest primarily in G1 in response to N-(phosphonacetyl)-l-aspartate (PALA), which starves them for pyrimidine nucleotides, and do not generate or tolerate amplification of the...

Effects of Genome Position and the DNA Damage Checkpoint on the Structure and Frequency of sod2 Gene Amplification in Fission Yeast

Patterson, Thomas E., Albrecht, Elizabeth B., Nurse, Paul, Sazer, Shelley, Stark, George R.

The Schizosaccharomyces pombe sod2 gene, located near the telomere on the long arm of chromosome I, encodes a Na+ (or Li+)/H+ antiporter. Amplification of sod2 has previously been shown to confer...

Mechanisms of G2 Arrest in Response to Overexpression of p53

Taylor, William R., DePrimo, Samuel E., Agarwal, Archana, Agarwal, Munna L., Schönthal, Axel H., Katula, Karen S., ...

Overexpression of p53 causes G2 arrest, attributable in part to the loss of CDC2 activity. Transcription of cdc2 and cyclin B1, determined using reporter constructs driven by the two promoters, was...

Act1, an NF-κB-activating protein

Li, Xiaoxia, Commane, Mairead, Nie, Huiqin, Hua, Xianxin, Chatterjee-Kishore, Moitreyee, Wald, David, ...

Use of an NF-κB-dependent selectable marker facilitated the isolation of a cell line containing a cDNA encoding Act1, an NF-κB activator. Act1 associates with and activates IκB kinase (IKK),...

CIITA stimulation of transcription factor binding to major histocompatibility complex class II and associated promoters in vivo

Wright, Kenneth L., Chin, Keh-Chuang, Linhoff, Michael, Skinner, Cheryl, Brown, Jeffrey A., Boss, Jeremy M., ...

CIITA is a master transactivator of the major histocompatibility complex class II genes, which are involved in antigen presentation. Defects in CIITA result in fatal immunodeficiencies. CIITA...

IL-1-induced NFκB and c-Jun N-terminal kinase (JNK) activation diverge at IL-1 receptor-associated kinase (IRAK)

Li, Xiaoxia, Commane, Mairead, Jiang, Zhengfan, Stark, George R.

Mutant I1A cells, lacking IL-1 receptor-associated kinase (IRAK) mRNA and protein, have been used to study the involvement of IRAK in NFκB and c-Jun N-terminal kinase (JNK) activation. A series of...

Stat1-independent regulation of gene expression in response to IFN-γ

Ramana, Chilakamarti V., Gil, M. Pilar, Han, Yulong, Ransohoff, Richard M., Schreiber, Robert D., Stark, George R.

Although Stat1 is essential for cells to respond fully to IFN-γ, there is substantial evidence that, in the absence of Stat1, IFN-γ can still regulate the expression of some genes, induce an...

Biologic consequences of Stat1-independent IFN signaling

Gil, M. Pilar, Bohn, Erwin, O'Guin, Andrew K., Ramana, Chilakamarti V., Levine, Beth, Stark, George R., ...

Although Stat1 is required for many IFN-dependent responses, recent work has shown that IFNγ functions independently of Stat1 to affect the growth of tumor cells or immortalized fibroblasts. We now...

Mutant Cells That Do Not Respond to Interleukin-1 (IL-1) Reveal a Novel Role for IL-1 Receptor-Associated Kinase

Li, Xiaoxia, Commane, Mairead, Burns, Carmel, Vithalani, Kalpa, Cao, Zhaodan, Stark, George R.

Mutagenized human 293 cells containing an interleukin-1 (IL-1)-regulated herpes thymidine kinase gene, selected in IL-1 and gancyclovir, have yielded many independent clones that are unresponsive to...

Activation of Phosphatidylinositol 3-Kinase in Response to Interleukin-1 Leads to Phosphorylation and Activation of the NF-κB p65/RelA Subunit

Sizemore, Nywana, Leung, Stewart, Stark, George R.

The work of Reddy et al. (S. A. Reddy, J. A. Huang, and W. S. Liao, J. Biol. Chem. 272:29167–29173, 1997) reveals that phosphatidylinositol 3-kinase (PI3K) plays a role in transducing a signal from...

Interleukin-1 (IL-1) Receptor-Associated Kinase Leads to Activation of TAK1 by Inducing TAB2 Translocation in the IL-1 Signaling Pathway

Takaesu, Giichi, Ninomiya-Tsuji, Jun, Kishida, Satoshi, Li, Xiaoxia, Stark, George R., Matsumoto, Kunihiro

Interleukin-1 (IL-1) is a proinflammatory cytokine that recognizes a surface receptor complex and generates multiple cellular responses. IL-1 stimulation activates the mitogen-activated protein...

MYC Abrogates p53-Mediated Cell Cycle Arrest in N-(Phosphonacetyl)-l-Aspartate-Treated Cells, Permitting CAD Gene Amplification

Chernova, Olga B., Chernov, Michail V., Ishizaka, Yukihito, Agarwal, Munna L., Stark, George R.

Genomic instability, including the ability to undergo gene amplification, is a hallmark of neoplastic cells. Similar to normal cells, “nonpermissive” REF52 cells do not develop resistance to...

IRF-3-dependent, NFκB- and JNK-independent activation of the 561 and IFN-β genes in response to double-stranded RNA

Peters, Kristi L., Smith, Heather L., Stark, George R., Sen, Ganes C.

Double-stranded (ds) RNA induces transcription of the 561 gene by activating IFN regulatory factor (IRF) transcription factors, whereas similar induction of the IFN-β gene is thought to require...

Stat1-Dependent, p53-Independent Expression of p21waf1 Modulates Oxysterol-Induced Apoptosis

Agrawal, Sudesh, Agarwal, Munna L., Chatterjee-Kishore, Moitreyee, Stark, George R., Chisolm, Guy M.

7-Ketocholesterol (7kchol) is prominent in atherosclerotic lesions where apoptosis occurs. Using mouse fibroblasts lacking p53, p21waf1, or Stat1, we found that optimal 7kchol-induced apoptosis...

The cell death regulator GRIM-19 is an inhibitor of signal transducer and activator of transcription 3

Zhang, Jun, Yang, Jinbo, Roy, Sanjit K., Tininini, Silvia, Hu, Jiadi, Bromberg, Jacqueline F., ...

GRIM-19 (gene associated with retinoid-IFN-induced mortality 19), isolated as a cell death activator in a genetic screen used to define mechanisms involved in IFN-β- and retinoic acid-induced cell...

Separation and Properties of Two Kinds of Simian Virus 40 Late Transcription Complexes

Llopis, Rafael, Stark, George R.

Simian virus 40 (SV40) transcription complexes were labeled in cells with 3-min pulses of [3H]uridine 48 h after infection and were extracted from nuclei in isotonic buffer or in a buffer containing...

Use of Dimethyl Suberimidate, a Cross-Linking Reagent, in Studying the Subunit Structure of Oligomeric Proteins*

Davies, Gregg E., Stark, George R.

Amidination of aldolase, glyceraldehyde-3-phosphate dehydrogenase, tryptophan synthetase B protein, L-arabinose isomerase, and the catalytic subunit of E. coli aspartate transcarbamylase with the...

Regulation of c–myc expression by IFN–γ through Stat1-dependent and -independent pathways

Ramana, Chilakamarti V., Grammatikakis, Nicholas, Chernov, Mikhail, Nguyen, Hannah, Goh, Kee Chuan, Williams, Bryan R.G., ...

Interferons (IFNs) inhibit cell growth in a Stat1-dependent fashion that involves regulation of c–myc expression. IFN–γ suppresses c–myc in wild-type mouse embryo fibroblasts, but not in...

How Stat1 mediates constitutive gene expression: a complex of unphosphorylated Stat1 and IRF1 supports transcription of the LMP2 gene

Chatterjee-Kishore, Moitreyee, Wright, Kenneth L., Ting, Jenny P.-Y., Stark, George R.

Analysis of mRNA levels in cells that express or lack signal transducers and activators of transcription 1 (Stat1) reveals that Stat1 mediates the constitutive transcription of many genes. Expression...

Mutant human cells with constitutive activation of NF-κB

Sathe, Swati S., Sizemore, Nywana, Li, Xiaoxia, Vithalani, Kalpa, Commane, Mairead, Swiatkowski, Shannon M., ...

We have used a genetic approach to generate eight different mutant human cell lines in which NF-κB is constitutively activated. These independent clones have different phenotypes and belong to...

Regulation of Simian Virus 40 Transcription: Sensitive Analysis of the RNA Species Present Early in Infections by Virus or Viral DNA

Parker, Barbara A., Stark, George R.

We have examined the discrete species of simian virus 40 (SV40) RNA present very early in infection of monkey cells with wild-type virus, with mutant tsA58 virus, and with the corresponding DNAs to...

Identification of a human NF-κB-activating protein, TAB3

Jin, Ge, Klika, Alison, Callahan, Michelle, Faga, Ben, Danzig, Joel, Jiang, Zhengfan, ...

The NF-κB pathway plays a critical role in regulating cellular processes such as immune responses, stress responses, apoptosis, proliferation and differentiation, whereas dysfunction of this pathway...

Secreted transforming growth factor β2 activates NF-κB, blocks apoptosis, and is essential for the survival of some tumor cells

Lu, Tao, Burdelya, Lyudmila G., Swiatkowski, Shannon M., Boiko, Alexander D., Howe, Philip H., Stark, George R., ...

The basis of constitutive activation of NF-κB, essential for survival and resistance to apoptosis in many tumors, is not well understood. We find that transforming growth factor β2 (TGFβ2),...

Inhibitor of κB kinase is required to activate a subset of interferon γ-stimulated genes

Sizemore, Nywana, Agarwal, Anju, Das, Kingshuk, Lerner, Natalia, Sulak, Michael, Rani, Sandhya, ...

IκB kinase (IKK), discovered as the major activator of NF-κB, plays additional roles in signaling. By using mouse embryo fibroblasts (MEFs) lacking both the α and β subunits of IKK, we find that...

Characterization of the Autoregulation of Simian Virus 40 Gene A

Alwine, James C., Reed, Steven I., Stark, George R.

Cells infected by tsA mutants of simian virus 40 (SV40) overproduce early RNA. Overproduction results from failure of the temperature-sensitive A protein (T antigen) to inhibit early transcription....

CARD4/Nod1 mediates NF-κB and JNK activation by invasive Shigella flexneri

Girardin, Stephen E., Tournebize, Régis, Mavris, Maria, Page, Anne-Laure, Li, Xiaoxia, Stark, George R., ...

Epithelial cells are refractory to extracellular lipopolysaccharide (LPS), yet when presented inside the cell, it is capable of initiating an inflammatory response. Using invasive Shigella flexneri...

Mutagenesis by reversible promoter insertion to study the activation of NF-κB

Kandel, Eugene S., Lu, Tao, Wan, Youzhong, Agarwal, Mukesh K., Jackson, Mark W., Stark, George R.

Genetic dissection of signaling pathways in mammalian cells involves screening or selecting phenotypic mutants obtained by a variety of techniques. Limitations in current methods include inadequate...

Down-Regulation of p53 by Double-Stranded RNA Modulates the Antiviral Response

Marques, Joao T., Rebouillat, Dominique, Ramana, Chilakamarti V., Murakami, Junko, Hill, Jason E., Gudkov, Andrei, ...

p53 has been well characterized as a tumor suppressor gene, but its role in antiviral defense remains unclear. A recent report has demonstrated that p53 can be induced by interferons and is activated...

Small molecules that reactivate p53 in renal cell carcinoma reveal a NF-κB-dependent mechanism of p53 suppression in tumors

Gurova, Katerina V., Hill, Jason E., Guo, Canhui, Prokvolit, Anatoly, Burdelya, Lyudmila G., Samoylova, Eugenia, ...

Renal cell carcinomas (RCC) commonly retain wild-type but functionally inactive p53, which is repressed by an unknown dominant mechanism. To help reveal this mechanism, we screened a diverse chemical...

Mechanisms of sod2 Gene Amplification in Schizosaccharomyces pombe

Albrecht, Elizabeth B., Hunyady, Aaron B., Stark, George R., Patterson, Thomas E.

Gene amplification in eukaryotes plays an important role in drug resistance, tumorigenesis, and evolution. The Schizosaccharomyces pombe sod2 gene provides a useful model system to analyze this...

Stabilization and activation of p53 are regulated independently by different phosphorylation events

Chernov, Mikhail V., Ramana, Chilakamarti V., Adler, Victor V., Stark, George R.

Treatment of mouse or human cells with the protein kinase C (PKC) inhibitors H7 or bisindolylmaleimide I induced an increase in the lifetime of p53, leading to its accumulation. In inhibitor-treated...

A mutant cell line defective in response to double-stranded RNA and in regulating basal expression of interferon-stimulated genes

Leaman, Douglas W., Salvekar, Anupama, Patel, Rekha, Sen, Ganes C., Stark, George R.

Although much progress has been made in identifying the signaling pathways that mediate the initial responses to interferons (IFNs), much less is known about how IFN-stimulated genes (ISGs) are kept...

Receptor-associated constitutive protein tyrosine phosphatase activity controls the kinase function of JAK1

Haque, S. Jaharul, Wu, Qian, Kammer, Winfried, Friedrich, Karlheinz, Smith, Jonathan M., Kerr, Ian M., ...

Exposure of cells to protein tyrosine phosphatase (PTP) inhibitors causes an increase in the phosphotyrosine content of many cellular proteins. However, the level at which the primary signaling event...

A p53-dependent S-phase checkpoint helps to protect cells from DNA damage in response to starvation for pyrimidine nucleotides

Agarwal, Munna L., Agarwal, Archana, Taylor, William R., Chernova, Olga, Sharma, Yogesh, Stark, George R.

Normal mammalian cells arrest primarily in G1 in response to N-(phosphonacetyl)-l-aspartate (PALA), which starves them for pyrimidine nucleotides, and do not generate or tolerate amplification of the...

Effects of Genome Position and the DNA Damage Checkpoint on the Structure and Frequency of sod2 Gene Amplification in Fission Yeast

Patterson, Thomas E., Albrecht, Elizabeth B., Nurse, Paul, Sazer, Shelley, Stark, George R.

The Schizosaccharomyces pombe sod2 gene, located near the telomere on the long arm of chromosome I, encodes a Na+ (or Li+)/H+ antiporter. Amplification of sod2 has previously been shown to confer...

Mechanisms of G2 Arrest in Response to Overexpression of p53

Taylor, William R., DePrimo, Samuel E., Agarwal, Archana, Agarwal, Munna L., Schönthal, Axel H., Katula, Karen S., ...

Overexpression of p53 causes G2 arrest, attributable in part to the loss of CDC2 activity. Transcription of cdc2 and cyclin B1, determined using reporter constructs driven by the two promoters, was...

Act1, an NF-κB-activating protein

Li, Xiaoxia, Commane, Mairead, Nie, Huiqin, Hua, Xianxin, Chatterjee-Kishore, Moitreyee, Wald, David, ...

Use of an NF-κB-dependent selectable marker facilitated the isolation of a cell line containing a cDNA encoding Act1, an NF-κB activator. Act1 associates with and activates IκB kinase (IKK),...

CIITA stimulation of transcription factor binding to major histocompatibility complex class II and associated promoters in vivo

Wright, Kenneth L., Chin, Keh-Chuang, Linhoff, Michael, Skinner, Cheryl, Brown, Jeffrey A., Boss, Jeremy M., ...

CIITA is a master transactivator of the major histocompatibility complex class II genes, which are involved in antigen presentation. Defects in CIITA result in fatal immunodeficiencies. CIITA...

IL-1-induced NFκB and c-Jun N-terminal kinase (JNK) activation diverge at IL-1 receptor-associated kinase (IRAK)

Li, Xiaoxia, Commane, Mairead, Jiang, Zhengfan, Stark, George R.

Mutant I1A cells, lacking IL-1 receptor-associated kinase (IRAK) mRNA and protein, have been used to study the involvement of IRAK in NFκB and c-Jun N-terminal kinase (JNK) activation. A series of...

Stat1-independent regulation of gene expression in response to IFN-γ

Ramana, Chilakamarti V., Gil, M. Pilar, Han, Yulong, Ransohoff, Richard M., Schreiber, Robert D., Stark, George R.

Although Stat1 is essential for cells to respond fully to IFN-γ, there is substantial evidence that, in the absence of Stat1, IFN-γ can still regulate the expression of some genes, induce an...

Biologic consequences of Stat1-independent IFN signaling

Gil, M. Pilar, Bohn, Erwin, O'Guin, Andrew K., Ramana, Chilakamarti V., Levine, Beth, Stark, George R., ...

Although Stat1 is required for many IFN-dependent responses, recent work has shown that IFNγ functions independently of Stat1 to affect the growth of tumor cells or immortalized fibroblasts. We now...

Mutant Cells That Do Not Respond to Interleukin-1 (IL-1) Reveal a Novel Role for IL-1 Receptor-Associated Kinase

Li, Xiaoxia, Commane, Mairead, Burns, Carmel, Vithalani, Kalpa, Cao, Zhaodan, Stark, George R.

Mutagenized human 293 cells containing an interleukin-1 (IL-1)-regulated herpes thymidine kinase gene, selected in IL-1 and gancyclovir, have yielded many independent clones that are unresponsive to...

Activation of Phosphatidylinositol 3-Kinase in Response to Interleukin-1 Leads to Phosphorylation and Activation of the NF-κB p65/RelA Subunit

Sizemore, Nywana, Leung, Stewart, Stark, George R.

The work of Reddy et al. (S. A. Reddy, J. A. Huang, and W. S. Liao, J. Biol. Chem. 272:29167–29173, 1997) reveals that phosphatidylinositol 3-kinase (PI3K) plays a role in transducing a signal from...

Interleukin-1 (IL-1) Receptor-Associated Kinase Leads to Activation of TAK1 by Inducing TAB2 Translocation in the IL-1 Signaling Pathway

Takaesu, Giichi, Ninomiya-Tsuji, Jun, Kishida, Satoshi, Li, Xiaoxia, Stark, George R., Matsumoto, Kunihiro

Interleukin-1 (IL-1) is a proinflammatory cytokine that recognizes a surface receptor complex and generates multiple cellular responses. IL-1 stimulation activates the mitogen-activated protein...

MYC Abrogates p53-Mediated Cell Cycle Arrest in N-(Phosphonacetyl)-l-Aspartate-Treated Cells, Permitting CAD Gene Amplification

Chernova, Olga B., Chernov, Michail V., Ishizaka, Yukihito, Agarwal, Munna L., Stark, George R.

Genomic instability, including the ability to undergo gene amplification, is a hallmark of neoplastic cells. Similar to normal cells, “nonpermissive” REF52 cells do not develop resistance to...

IRF-3-dependent, NFκB- and JNK-independent activation of the 561 and IFN-β genes in response to double-stranded RNA

Peters, Kristi L., Smith, Heather L., Stark, George R., Sen, Ganes C.

Double-stranded (ds) RNA induces transcription of the 561 gene by activating IFN regulatory factor (IRF) transcription factors, whereas similar induction of the IFN-β gene is thought to require...

Stat1-Dependent, p53-Independent Expression of p21waf1 Modulates Oxysterol-Induced Apoptosis

Agrawal, Sudesh, Agarwal, Munna L., Chatterjee-Kishore, Moitreyee, Stark, George R., Chisolm, Guy M.

7-Ketocholesterol (7kchol) is prominent in atherosclerotic lesions where apoptosis occurs. Using mouse fibroblasts lacking p53, p21waf1, or Stat1, we found that optimal 7kchol-induced apoptosis...

The cell death regulator GRIM-19 is an inhibitor of signal transducer and activator of transcription 3

Zhang, Jun, Yang, Jinbo, Roy, Sanjit K., Tininini, Silvia, Hu, Jiadi, Bromberg, Jacqueline F., ...

GRIM-19 (gene associated with retinoid-IFN-induced mortality 19), isolated as a cell death activator in a genetic screen used to define mechanisms involved in IFN-β- and retinoic acid-induced cell...

Separation and Properties of Two Kinds of Simian Virus 40 Late Transcription Complexes

Llopis, Rafael, Stark, George R.

Simian virus 40 (SV40) transcription complexes were labeled in cells with 3-min pulses of [3H]uridine 48 h after infection and were extracted from nuclei in isotonic buffer or in a buffer containing...

Use of Dimethyl Suberimidate, a Cross-Linking Reagent, in Studying the Subunit Structure of Oligomeric Proteins*

Davies, Gregg E., Stark, George R.

Amidination of aldolase, glyceraldehyde-3-phosphate dehydrogenase, tryptophan synthetase B protein, L-arabinose isomerase, and the catalytic subunit of E. coli aspartate transcarbamylase with the...

Regulation of c–myc expression by IFN–γ through Stat1-dependent and -independent pathways

Ramana, Chilakamarti V., Grammatikakis, Nicholas, Chernov, Mikhail, Nguyen, Hannah, Goh, Kee Chuan, Williams, Bryan R.G., ...

Interferons (IFNs) inhibit cell growth in a Stat1-dependent fashion that involves regulation of c–myc expression. IFN–γ suppresses c–myc in wild-type mouse embryo fibroblasts, but not in...

How Stat1 mediates constitutive gene expression: a complex of unphosphorylated Stat1 and IRF1 supports transcription of the LMP2 gene

Chatterjee-Kishore, Moitreyee, Wright, Kenneth L., Ting, Jenny P.-Y., Stark, George R.

Analysis of mRNA levels in cells that express or lack signal transducers and activators of transcription 1 (Stat1) reveals that Stat1 mediates the constitutive transcription of many genes. Expression...

Mutant human cells with constitutive activation of NF-κB

Sathe, Swati S., Sizemore, Nywana, Li, Xiaoxia, Vithalani, Kalpa, Commane, Mairead, Swiatkowski, Shannon M., ...

We have used a genetic approach to generate eight different mutant human cell lines in which NF-κB is constitutively activated. These independent clones have different phenotypes and belong to...

Regulation of Simian Virus 40 Transcription: Sensitive Analysis of the RNA Species Present Early in Infections by Virus or Viral DNA

Parker, Barbara A., Stark, George R.

We have examined the discrete species of simian virus 40 (SV40) RNA present very early in infection of monkey cells with wild-type virus, with mutant tsA58 virus, and with the corresponding DNAs to...

Identification of a human NF-κB-activating protein, TAB3

Jin, Ge, Klika, Alison, Callahan, Michelle, Faga, Ben, Danzig, Joel, Jiang, Zhengfan, ...

The NF-κB pathway plays a critical role in regulating cellular processes such as immune responses, stress responses, apoptosis, proliferation and differentiation, whereas dysfunction of this pathway...

Secreted transforming growth factor β2 activates NF-κB, blocks apoptosis, and is essential for the survival of some tumor cells

Lu, Tao, Burdelya, Lyudmila G., Swiatkowski, Shannon M., Boiko, Alexander D., Howe, Philip H., Stark, George R., ...

The basis of constitutive activation of NF-κB, essential for survival and resistance to apoptosis in many tumors, is not well understood. We find that transforming growth factor β2 (TGFβ2),...

Inhibitor of κB kinase is required to activate a subset of interferon γ-stimulated genes

Sizemore, Nywana, Agarwal, Anju, Das, Kingshuk, Lerner, Natalia, Sulak, Michael, Rani, Sandhya, ...

IκB kinase (IKK), discovered as the major activator of NF-κB, plays additional roles in signaling. By using mouse embryo fibroblasts (MEFs) lacking both the α and β subunits of IKK, we find that...

Characterization of the Autoregulation of Simian Virus 40 Gene A

Alwine, James C., Reed, Steven I., Stark, George R.

Cells infected by tsA mutants of simian virus 40 (SV40) overproduce early RNA. Overproduction results from failure of the temperature-sensitive A protein (T antigen) to inhibit early transcription....

CARD4/Nod1 mediates NF-κB and JNK activation by invasive Shigella flexneri

Girardin, Stephen E., Tournebize, Régis, Mavris, Maria, Page, Anne-Laure, Li, Xiaoxia, Stark, George R., ...

Epithelial cells are refractory to extracellular lipopolysaccharide (LPS), yet when presented inside the cell, it is capable of initiating an inflammatory response. Using invasive Shigella flexneri...

Mutagenesis by reversible promoter insertion to study the activation of NF-κB

Kandel, Eugene S., Lu, Tao, Wan, Youzhong, Agarwal, Mukesh K., Jackson, Mark W., Stark, George R.

Genetic dissection of signaling pathways in mammalian cells involves screening or selecting phenotypic mutants obtained by a variety of techniques. Limitations in current methods include inadequate...

Down-Regulation of p53 by Double-Stranded RNA Modulates the Antiviral Response

Marques, Joao T., Rebouillat, Dominique, Ramana, Chilakamarti V., Murakami, Junko, Hill, Jason E., Gudkov, Andrei, ...

p53 has been well characterized as a tumor suppressor gene, but its role in antiviral defense remains unclear. A recent report has demonstrated that p53 can be induced by interferons and is activated...

Small molecules that reactivate p53 in renal cell carcinoma reveal a NF-κB-dependent mechanism of p53 suppression in tumors

Gurova, Katerina V., Hill, Jason E., Guo, Canhui, Prokvolit, Anatoly, Burdelya, Lyudmila G., Samoylova, Eugenia, ...

Renal cell carcinomas (RCC) commonly retain wild-type but functionally inactive p53, which is repressed by an unknown dominant mechanism. To help reveal this mechanism, we screened a diverse chemical...

Macrophage inhibitory cytokine 1 mediates a p53-dependent protective arrest in S phase in response to starvation for DNA precursors

Agarwal, Mukesh K., Hastak, Kedar, Jackson, Mark W., Breit, Samuel N., Stark, George R., Agarwal, Munna L.

p53 is essential for the cellular responses to DNA damage that help to maintain genomic stability. Protective p53-dependent cell-cycle checkpoints are activated in response to a wide variety of...

Dose-dependent cross-talk between the transforming growth factor-β and interleukin-1 signaling pathways

Lu, Tao, Tian, Liping, Han, Yulong, Vogelbaum, Michael, Stark, George R.

Some tumor cell lines secrete high concentrations of TGFβ or IL-1. Similarly high concentrations of each of these cytokines cross-activate the other pathway: TGFβ activates NFκB, and IL-1β...

Unphosphorylated STAT3 accumulates in response to IL-6 and activates transcription by binding to NFκB

Yang, Jinbo, Liao, Xudong, Agarwal, Mukesh K., Barnes, Laura, Auron, Philip E., Stark, George R.

gp130-linked cytokines such as interleukin-6 (IL-6) stimulate the formation of tyrosine-phosphorylated signal transducer and activator of transcription 3 (P-STAT3), which activates many genes,...

DNA synthesis from unbalanced nucleotide pools causes limited DNA damage that triggers ATR-CHK1-dependent p53 activation

Hastak, Kedar, Paul, Rajib K., Agarwal, Mukesh K., Thakur, Vijay S., Agrawal, Sudesh, ...

p53-dependent G1 and G2 cell cycle checkpoints are activated in response DNA damage that help to maintain genomic stability. p53 also helps to protect cells from damage that occurs during S phase,...

Unphosphorylated STAT1 prolongs the expression of interferon-induced immune regulatory genes

Cheon, HyeonJoo, Stark, George R.

In normal human cells treated with interferons (IFNs), the concentration of tyrosine-phosphorylated STAT1 (YP-STAT1), which drives the expression of a large number of genes, increases quickly but...

Validation-based insertional mutagenesis identifies lysine demethylase FBXL11 as a negative regulator of NFκB

Lu, Tao, Jackson, Mark W., Singhi, Aatur D., Kandel, Eugene S., Yang, Maojing, Zhang, Yi, ...

We describe a highly efficient use of lentiviral validation-based insertional mutagenesis (VBIM) to generate large populations of mammalian cells in which a strong promoter is inserted into many...