Stanley J. Korsmeyer

Publication List Details

Period

1991 - 2007

Number

80

Co-Authors

Multiple signaling pathways promote B lymphocyte stimulator dependent B-cell growth and survival (2007)

Woodland, Robert T., Fox, Casey J., Schmidt, Madelyn R., Hammerman, Peter S., Opferman, Joseph T., Korsmeyer, Stanley J., ...

We investigated the mechanism by which B lymphocyte stimulator (BLyS)/BAFF, a tumor necrosis factor superfamily ligand, promotes B-cell survival and resistance to atrophy. BLyS stimulation activates...

Proteolysis of MLL family proteins is essential for Taspase1-orchestrated cell cycle progression (2006)

Takeda, Shugaku, Chen, David Y., Westergard, Todd D., Fisher, Jill K., Rubens, Jeffrey A., Sasagawa, Satoru, ...

Taspase1 was identified as the threonine endopeptidase that cleaves mixed-lineage leukemia (MLL) for proper Hox gene expression in vitro. To investigate its functions in vivo, we generated...

Bax channel inhibitors prevent mitochondrion-mediated apoptosis and protect neurons in a model of global brain ischemia (2005)

Hetz, Claudio, Vitte, Pierre-Alain, Bombrun, Agnes, Rostovtseva, Tatiana K., Hiver, Agnes, Schwarz, Matthias K., ...

Ischemic injuries are associated with several pathological conditions, including stroke and myocardial infarction. Several studies have indicated extensive apoptotic cell death in the infarcted area...

Regulation of B cell survival in xid mice by the proto-oncogene bcl-2 (1996)

Woodland, Robert T., Schmidt, Madelyn R., Korsmeyer, Stanley J., Gravel, Kathryn A.

CBA/N mice carry an X-linked immunodeficiency (xid) due to a point mutation in the Bruton's tyrosine kinase (btk) gene. xid mice have a smaller peripheral B cell pool than normal animals, lack CD5+ B...

Radiation-induced apoptosis is differentially regulated in primary B cells from normal mice and mice with the CBA/N X-linked immunodeficiency (1995)

Woodland, Robert T., Schmidt, Madelyn R., Riggs, James E., Korsmeyer, Stanley J., Lussier, Annette M., Gravel, Kathryn A.

Normal B cells responsive to thymus independent-type 1 Ags (TI-1) are resistant to low doses of ionizing radiation in vivo (200-300 cGy), compared with TI-1 responsive B cells of mice with the CBA/N...

Skewed B cell VH family repertoire in Bcl-2- transgenic mice (1991)

Yeh, Trai-Ming, Korsmeyer, Stanley J., Teale, Judy M.

The proto-oncogene Bcl-2 is normally expressed in B lineage cells in a stage specific manner and extends cell survival. Deregulated Bcl-2 expression has been shown to cause a major expansion in...

Atm and Bax cooperate in ionizing radiation-induced apoptosis in the central nervous system

Chong, Miriam J., Murray, Michael R., Gosink, Eric C., Russell, Helen R. C., Srinivasan, Anu, Kapsetaki, Manuela, ...

Ataxia-telangiectasia is a hereditary multisystemic disease resulting from mutations of ataxia telangiectasia, mutated (ATM) and is characterized by neurodegeneration, cancer, immune defects, and...

bax-deficiency promotes drug resistance and oncogenic transformation by attenuating p53-dependent apoptosis

McCurrach, Mila E., Connor, Thomas M. F., Knudson, C. Michael, Korsmeyer, Stanley J., Lowe, Scott W.

Inactivation of p53-dependent apoptosis promotes oncogenic transformation, tumor development, and resistance to many cytotoxic anticancer agents. p53 can transcriptionally activate bax, a bcl-2...

Comparison of the ion channel characteristics of proapoptotic BAX and antiapoptotic BCL-2

Schlesinger, Paul H., Gross, Atan, Yin, Xiao-Ming, Yamamoto, Kazuhito, Saito, Mitsuyoshi, Waksman, Gabriel, ...

The BCL-2 family of proteins is composed of both pro- and antiapoptotic regulators, although its most critical biochemical functions remain uncertain. The structural similarity between the BCL-XL...

Mammalian Trithorax and Polycomb-group homologues are antagonistic regulators of homeotic development

Hanson, Robin D., Hess, Jay L., Yu, Benjamin D., Ernst, Patricia, Van Lohuizen, Maarten, Berns, Anton, ...

Control of cell identity during development is specified in large part by the unique expression patterns of multiple homeobox-containing (Hox) genes in specific segments of an embryo. Trithorax and...

MLL, a mammalian trithorax-group gene, functions as a transcriptional maintenance factor in morphogenesis

Yu, Benjamin D., Hanson, Robin D., Hess, Jay L., Horning, Susan E., Korsmeyer, Stanley J.

Determinative events in vertebrate embryogenesis appear to require the continuous expression of spatial regulators such as the clustered homeobox genes. The mechanisms that govern long-term patterns...

Bax ablation prevents dopaminergic neurodegeneration in the 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease

Vila, Miquel, Jackson-Lewis, Vernice, Vukosavic, Slobodanka, Djaldetti, Ruth, Liberatore, Gabriel, Offen, Daniel, ...

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) damages dopaminergic neurons in the substantia nigra pars compacta (SNpc) as seen in Parkinson's disease. Here, we show that the pro-apoptotic...

p70S6 kinase signals cell survival as well as growth, inactivating the pro-apoptotic molecule BAD

Harada, Hisashi, Andersen, Jens S., Mann, Matthias, Terada, Naohiro, Korsmeyer, Stanley J.

Cytokines often deliver simultaneous, yet distinct, cell growth and cell survival signals. The 70-kDa ribosomal protein S6 kinase (p70S6K) is known to regulate cell growth by inducing protein...

Granzyme B can cause mitochondrial depolarization and cell death in the absence of BID, BAX, and BAK

Thomas, Dori A., Scorrano, Luca, Putcha, Girish V., Korsmeyer, Stanley J., Ley, Timothy J.

Granzyme B (GzmB) is a serine protease that is used by activated cytotoxic T lymphocytes to induce target cell apoptosis. Although GzmB directly cleaves the Bcl2 family member BID on target cell...

BID mediates neuronal cell death after oxygen/ glucose deprivation and focal cerebral ischemia

Plesnila, Nikolaus, Zinkel, Sandra, Le, Dean A., Amin-Hanjani, Sepideh, Wu, Yonqin, Qiu, Jianhua, ...

Mitochondria and cytochrome c release play a role in the death of neurons and glia after cerebral ischemia. In the present study, we investigated whether BID, a proapoptotic promoter of cytochrome c...

BCL-2 Is Phosphorylated and Inactivated by an ASK1/Jun N-Terminal Protein Kinase Pathway Normally Activated at G2/M

Yamamoto, Kazuhito, Ichijo, Hidenori, Korsmeyer, Stanley J.

Multiple signal transduction pathways are capable of modifying BCL-2 family members to reset susceptibility to apoptosis. We used two-dimensional peptide mapping and sequencing to identify three...

Biochemical and Genetic Analysis of the Mitochondrial Response of Yeast to BAX and BCL-XL

Gross, Atan, Pilcher, Kirsten, Blachly-Dyson, Elizabeth, Basso, Emy, Jockel, Jennifer, Bassik, Michael C., ...

The BCL-2 family includes both proapoptotic (e.g., BAX and BAK) and antiapoptotic (e.g., BCL-2 and BCL-XL) molecules. The cell death-regulating activity of BCL-2 members appears to depend on their...

Jak3 Selectively Regulates Bax and Bcl-2 Expression To Promote T-Cell Development

Wen, Renren, Wang, Demin, McKay, Catriona, Bunting, Kevin D., Marine, Jean-Christophe, Vanin, Elio F., ...

Jak3-deficient mice display vastly reduced numbers of lymphoid cells. Thymocytes and peripheral T cells from Jak3-deficient mice have a high apoptotic index, suggesting that Jak3 provides survival...

MLL and CREB Bind Cooperatively to the Nuclear Coactivator CREB-Binding Protein

Ernst, Patricia, Wang, Jing, Huang, Mary, Goodman, Richard H., Korsmeyer, Stanley J.

A fragment of the mixed-lineage leukemia (MLL) gene (Mll, HRX, ALL-1) was identified in a yeast genetic screen designed to isolate proteins that interact with the CREB–CREB-binding protein (CBP)...

Bax Loss Impairs Myc-Induced Apoptosis and Circumvents the Selection of p53 Mutations during Myc-Mediated Lymphomagenesis

Eischen, Christine M., Roussel, Martine F., Korsmeyer, Stanley J., Cleveland, John L.

The ARF and p53 tumor suppressors mediate Myc-induced apoptosis and suppress lymphoma development in Eμ-myc transgenic mice. Here we report that the proapoptotic Bcl-2 family member Bax also...

Involvement of Microtubules in the Regulation of Bcl2 Phosphorylation and Apoptosis through Cyclic AMP-Dependent Protein Kinase

Srivastava, Rakesh K., Srivastava, Aparna R., Korsmeyer, Stanley J., Nesterova, Maria, Cho-Chung, Yoon S., Longo, Dan L.

The Bcl2 family of proteins plays a significant role in regulation of apoptosis. In this study, the microtubule-damaging drugs paclitaxel, vincristine, and vinblastine induced Bcl2...

Mutagenesis of the BH3 Domain of BAX Identifies Residues Critical for Dimerization and Killing

Wang, Kun, Gross, Atan, Waksman, Gabriel, Korsmeyer, Stanley J.

The BCL-2 family of proteins is comprised of proapoptotic as well as antiapoptotic members (S. N. Farrow and R. Brown, Curr. Opin. Genet. Dev. 6:45–49, 1996). A prominent death agonist, BAX, forms...

Proteolytic Cleavage of MLL Generates a Complex of N- and C-Terminal Fragments That Confers Protein Stability and Subnuclear Localization

Hsieh, James J.-D., Ernst, Patricia, Erdjument-Bromage, Hediye, Tempst, Paul, Korsmeyer, Stanley J.

The mixed-lineage leukemia gene (MLL, ALL1, HRX) encodes a 3,969-amino-acid nuclear protein homologous to Drosophila trithorax and is required to maintain proper Hox gene expression. Chromosome...

A reversible component of mitochondrial respiratory dysfunction in apoptosis can be rescued by exogenous cytochrome c

Mootha, Vamsi K., Wei, Michael C., Buttle, Karolyn F., Scorrano, Luca, Panoutsakopoulou, Vily, Mannella, Carmen A., ...

Multiple apoptotic pathways release cytochrome c from the mitochondrial intermembrane space, resulting in the activation of downstream caspases. In vivo activation of Fas (CD95) resulted in...

Bad-deficient mice develop diffuse large B cell lymphoma

Ranger, Ann M., Zha, Jiping, Harada, Hisashi, Datta, Sandeep Robert, Danial, Nika N., Gilmore, Andrew P., ...

The proapoptotic activity of the “BH3-only” molecule BAD can be differentially regulated by survival factor signaling. Bad-deficient mice lacking both BAD long and BAD short proteins proved...

Proapoptotic BID is required for myeloid homeostasis and tumor suppression

Zinkel, Sandra S., Ong, Christy C., Ferguson, David O., Iwasaki, Hiromi, Akashi, Koichi, Bronson, Roderick T., ...

The proper expansion and contraction of hematopoietic cells requires tight regulation of cell death. BID, a “BH3-only” molecule, amplifies death receptor signals connecting the extrinsic to...

Mcl-1 deficiency results in peri-implantation embryonic lethality

Rinkenberger, Julie L., Horning, Susan, Klocke, Barbara, Roth, Kevin, Korsmeyer, Stanley J.

We disrupted the Mcl-1 locus in murine ES cells to determine the developmental roles of this Bcl-2 family member. Deletion of Mcl-1 resulted in peri-implantation embryonic lethality. Mcl-1−/−...

tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c

Wei, Michael C., Lindsten, Tullia, Mootha, Vamsi K., Weiler, Solly, Gross, Atan, Ashiya, Mona, ...

TNFR1/Fas engagement results in the cleavage of cytosolic BID to truncated tBID, which translocates to mitochondria. Immunodepletion and gene disruption indicate BID is required for cytochrome c...

Phosphorylation of BCL-2 regulates ER Ca2+ homeostasis and apoptosis

Bassik, Michael C, Scorrano, Luca, Oakes, Scott A, Pozzan, Tullio, Korsmeyer, Stanley J

Phosphorylation of BCL-2 within an unstructured loop inhibits its antiapoptotic effect. We found that phosphorylated BCL-2 predominantly localized to the endoplasmic reticulum (ER) and tested whether...

Survival factor-induced extracellular signal-regulated kinase phosphorylates BIM, inhibiting its association with BAX and proapoptotic activity

Harada, Hisashi, Quearry, Bonnie, Ruiz-Vela, Antonio, Korsmeyer, Stanley J.

The “BH3-only” proapoptotic BCL-2 family members initiate the intrinsic apoptotic pathway. A small interfering RNA knockdown of BIM confirms this BH3-only member is important for the...

Proapoptotic BAX and BAK regulate the type 1 inositol trisphosphate receptor and calcium leak from the endoplasmic reticulum

Oakes, Scott A., Scorrano, Luca, Opferman, Joseph T., Bassik, Michael C., Nishino, Mari, Pozzan, Tullio, ...

Proapoptotic BCL-2 family members BAX and BAK are required for the initiation of mitochondrial dysfunction during apoptosis and for maintaining the endoplasmic reticulum (ER) Ca2+ stores necessary...

Conditional MLL-CBP targets GMP and models therapy-related myeloproliferative disease

Wang, Jing, Iwasaki, Hiromi, Krivtsov, Andrei, Febbo, Phillip G, Thorner, Aaron R, Ernst, Patricia, ...

Chromosomal translocations that fuse the mixed lineage leukemia (MLL) gene with multiple partners typify acute leukemias of infancy as well as therapy-related leukemias. We utilized a conditional...

Oligomeric Bax Is a Component of the Putative Cytochrome c Release Channel MAC, Mitochondrial Apoptosis-induced Channel

Dejean, Laurent M., Martinez-Caballero, Sonia, Guo, Liang, Hughes, Cynthia, Teijido, Oscar, Ducret, Thomas, ...

Bcl-2 family proteins regulate apoptosis, in part, by controlling formation of the mitochondrial apoptosis-induced channel (MAC), which is a putative cytochrome c release channel induced early in the...

Essential role of BAX,BAK in B cell homeostasis and prevention of autoimmune disease

Takeuchi, Osamu, Fisher, Jill, Suh, Heikyung, Harada, Hisashi, Malynn, Barbara A., Korsmeyer, Stanley J.

B cell homeostasis is maintained by a balance between the continual generation of new cells and their elimination. Here we show proapoptotic BCL-2 family members BAX and BAK are essential for...

Cyclophilin D is a component of mitochondrial permeability transition and mediates neuronal cell death after focal cerebral ischemia

Schinzel, Anna C., Takeuchi, Osamu, Huang, Zhihong, Fisher, Jill K., Zhou, Zhipeng, Rubens, Jeffery, ...

Mitochondrial permeability transition (PT) is a phenomenon induced by high levels of matrix calcium and is characterized by the opening of the PT pore (PTP). Activation of the PTP results in loss of...

Activation of Apoptosis in Vivo by a Hydrocarbon-Stapled BH3 Helix

Walensky, Loren D., Kung, Andrew L., Escher, Iris, Malia, Thomas J., Barbuto, Scott, Wright, Renee D., ...

BCL-2 family proteins constitute a critical control point for the regulation of apoptosis. Protein interaction between BCL-2 members is a prominent mechanism of control and is mediated through the...

Proapoptotic BAX and BAK control multiple initiator caspases

Ruiz-Vela, Antonio, Opferman, Joseph T, Cheng, Emily H-Y, Korsmeyer, Stanley J

BAX and BAK operate at both the mitochondria and endoplasmic reticulum (ER) to regulate the intrinsic apoptotic pathway. An unresolved issue is whether any caspases can be activated in response to...

p600, a unique protein required for membrane morphogenesis and cell survival

Nakatani, Yoshihiro, Konishi, Hiroaki, Vassilev, Alex, Kurooka, Hisanori, Ishiguro, Keiichiro, Sawada, Jun-ichi, ...

In this article, we identify and characterize p600, a unique 600-kDa retinoblastoma protein- and calmodulin-binding protein. In the nucleus, p600 and retinoblastoma protein seem to act as a chromatin...

Uncleaved TFIIA Is a Substrate for Taspase 1 and Active in Transcription

Zhou, Huiqing, Spicuglia, Salvatore, Hsieh, James J.-D., Mitsiou, Dimitra J., Høiby, Torill, Veenstra, Gert Jan C., ...

In higher eukaryotes, the large subunit of the general transcription factor TFIIA is encoded by the single TFIIAαβ gene and posttranslationally cleaved into α and β subunits. The molecular...

Atm and Bax cooperate in ionizing radiation-induced apoptosis in the central nervous system

Chong, Miriam J., Murray, Michael R., Gosink, Eric C., Russell, Helen R. C., Srinivasan, Anu, Kapsetaki, Manuela, ...

Ataxia-telangiectasia is a hereditary multisystemic disease resulting from mutations of ataxia telangiectasia, mutated (ATM) and is characterized by neurodegeneration, cancer, immune defects, and...

bax-deficiency promotes drug resistance and oncogenic transformation by attenuating p53-dependent apoptosis

McCurrach, Mila E., Connor, Thomas M. F., Knudson, C. Michael, Korsmeyer, Stanley J., Lowe, Scott W.

Inactivation of p53-dependent apoptosis promotes oncogenic transformation, tumor development, and resistance to many cytotoxic anticancer agents. p53 can transcriptionally activate bax, a bcl-2...

Comparison of the ion channel characteristics of proapoptotic BAX and antiapoptotic BCL-2

Schlesinger, Paul H., Gross, Atan, Yin, Xiao-Ming, Yamamoto, Kazuhito, Saito, Mitsuyoshi, Waksman, Gabriel, ...

The BCL-2 family of proteins is composed of both pro- and antiapoptotic regulators, although its most critical biochemical functions remain uncertain. The structural similarity between the BCL-XL...

Mammalian Trithorax and Polycomb-group homologues are antagonistic regulators of homeotic development

Hanson, Robin D., Hess, Jay L., Yu, Benjamin D., Ernst, Patricia, Van Lohuizen, Maarten, Berns, Anton, ...

Control of cell identity during development is specified in large part by the unique expression patterns of multiple homeobox-containing (Hox) genes in specific segments of an embryo. Trithorax and...

MLL, a mammalian trithorax-group gene, functions as a transcriptional maintenance factor in morphogenesis

Yu, Benjamin D., Hanson, Robin D., Hess, Jay L., Horning, Susan E., Korsmeyer, Stanley J.

Determinative events in vertebrate embryogenesis appear to require the continuous expression of spatial regulators such as the clustered homeobox genes. The mechanisms that govern long-term patterns...

Bax ablation prevents dopaminergic neurodegeneration in the 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease

Vila, Miquel, Jackson-Lewis, Vernice, Vukosavic, Slobodanka, Djaldetti, Ruth, Liberatore, Gabriel, Offen, Daniel, ...

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) damages dopaminergic neurons in the substantia nigra pars compacta (SNpc) as seen in Parkinson's disease. Here, we show that the pro-apoptotic...

p70S6 kinase signals cell survival as well as growth, inactivating the pro-apoptotic molecule BAD

Harada, Hisashi, Andersen, Jens S., Mann, Matthias, Terada, Naohiro, Korsmeyer, Stanley J.

Cytokines often deliver simultaneous, yet distinct, cell growth and cell survival signals. The 70-kDa ribosomal protein S6 kinase (p70S6K) is known to regulate cell growth by inducing protein...

Granzyme B can cause mitochondrial depolarization and cell death in the absence of BID, BAX, and BAK

Thomas, Dori A., Scorrano, Luca, Putcha, Girish V., Korsmeyer, Stanley J., Ley, Timothy J.

Granzyme B (GzmB) is a serine protease that is used by activated cytotoxic T lymphocytes to induce target cell apoptosis. Although GzmB directly cleaves the Bcl2 family member BID on target cell...

BID mediates neuronal cell death after oxygen/ glucose deprivation and focal cerebral ischemia

Plesnila, Nikolaus, Zinkel, Sandra, Le, Dean A., Amin-Hanjani, Sepideh, Wu, Yonqin, Qiu, Jianhua, ...

Mitochondria and cytochrome c release play a role in the death of neurons and glia after cerebral ischemia. In the present study, we investigated whether BID, a proapoptotic promoter of cytochrome c...

BCL-2 Is Phosphorylated and Inactivated by an ASK1/Jun N-Terminal Protein Kinase Pathway Normally Activated at G2/M

Yamamoto, Kazuhito, Ichijo, Hidenori, Korsmeyer, Stanley J.

Multiple signal transduction pathways are capable of modifying BCL-2 family members to reset susceptibility to apoptosis. We used two-dimensional peptide mapping and sequencing to identify three...

Biochemical and Genetic Analysis of the Mitochondrial Response of Yeast to BAX and BCL-XL

Gross, Atan, Pilcher, Kirsten, Blachly-Dyson, Elizabeth, Basso, Emy, Jockel, Jennifer, Bassik, Michael C., ...

The BCL-2 family includes both proapoptotic (e.g., BAX and BAK) and antiapoptotic (e.g., BCL-2 and BCL-XL) molecules. The cell death-regulating activity of BCL-2 members appears to depend on their...

Jak3 Selectively Regulates Bax and Bcl-2 Expression To Promote T-Cell Development

Wen, Renren, Wang, Demin, McKay, Catriona, Bunting, Kevin D., Marine, Jean-Christophe, Vanin, Elio F., ...

Jak3-deficient mice display vastly reduced numbers of lymphoid cells. Thymocytes and peripheral T cells from Jak3-deficient mice have a high apoptotic index, suggesting that Jak3 provides survival...

MLL and CREB Bind Cooperatively to the Nuclear Coactivator CREB-Binding Protein

Ernst, Patricia, Wang, Jing, Huang, Mary, Goodman, Richard H., Korsmeyer, Stanley J.

A fragment of the mixed-lineage leukemia (MLL) gene (Mll, HRX, ALL-1) was identified in a yeast genetic screen designed to isolate proteins that interact with the CREB–CREB-binding protein (CBP)...

Bax Loss Impairs Myc-Induced Apoptosis and Circumvents the Selection of p53 Mutations during Myc-Mediated Lymphomagenesis

Eischen, Christine M., Roussel, Martine F., Korsmeyer, Stanley J., Cleveland, John L.

The ARF and p53 tumor suppressors mediate Myc-induced apoptosis and suppress lymphoma development in Eμ-myc transgenic mice. Here we report that the proapoptotic Bcl-2 family member Bax also...

Involvement of Microtubules in the Regulation of Bcl2 Phosphorylation and Apoptosis through Cyclic AMP-Dependent Protein Kinase

Srivastava, Rakesh K., Srivastava, Aparna R., Korsmeyer, Stanley J., Nesterova, Maria, Cho-Chung, Yoon S., Longo, Dan L.

The Bcl2 family of proteins plays a significant role in regulation of apoptosis. In this study, the microtubule-damaging drugs paclitaxel, vincristine, and vinblastine induced Bcl2...

Mutagenesis of the BH3 Domain of BAX Identifies Residues Critical for Dimerization and Killing

Wang, Kun, Gross, Atan, Waksman, Gabriel, Korsmeyer, Stanley J.

The BCL-2 family of proteins is comprised of proapoptotic as well as antiapoptotic members (S. N. Farrow and R. Brown, Curr. Opin. Genet. Dev. 6:45–49, 1996). A prominent death agonist, BAX, forms...

Proteolytic Cleavage of MLL Generates a Complex of N- and C-Terminal Fragments That Confers Protein Stability and Subnuclear Localization

Hsieh, James J.-D., Ernst, Patricia, Erdjument-Bromage, Hediye, Tempst, Paul, Korsmeyer, Stanley J.

The mixed-lineage leukemia gene (MLL, ALL1, HRX) encodes a 3,969-amino-acid nuclear protein homologous to Drosophila trithorax and is required to maintain proper Hox gene expression. Chromosome...

A reversible component of mitochondrial respiratory dysfunction in apoptosis can be rescued by exogenous cytochrome c

Mootha, Vamsi K., Wei, Michael C., Buttle, Karolyn F., Scorrano, Luca, Panoutsakopoulou, Vily, Mannella, Carmen A., ...

Multiple apoptotic pathways release cytochrome c from the mitochondrial intermembrane space, resulting in the activation of downstream caspases. In vivo activation of Fas (CD95) resulted in...

Bad-deficient mice develop diffuse large B cell lymphoma

Ranger, Ann M., Zha, Jiping, Harada, Hisashi, Datta, Sandeep Robert, Danial, Nika N., Gilmore, Andrew P., ...

The proapoptotic activity of the “BH3-only” molecule BAD can be differentially regulated by survival factor signaling. Bad-deficient mice lacking both BAD long and BAD short proteins proved...

Proapoptotic BID is required for myeloid homeostasis and tumor suppression

Zinkel, Sandra S., Ong, Christy C., Ferguson, David O., Iwasaki, Hiromi, Akashi, Koichi, Bronson, Roderick T., ...

The proper expansion and contraction of hematopoietic cells requires tight regulation of cell death. BID, a “BH3-only” molecule, amplifies death receptor signals connecting the extrinsic to...

Mcl-1 deficiency results in peri-implantation embryonic lethality

Rinkenberger, Julie L., Horning, Susan, Klocke, Barbara, Roth, Kevin, Korsmeyer, Stanley J.

We disrupted the Mcl-1 locus in murine ES cells to determine the developmental roles of this Bcl-2 family member. Deletion of Mcl-1 resulted in peri-implantation embryonic lethality. Mcl-1−/−...

tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c

Wei, Michael C., Lindsten, Tullia, Mootha, Vamsi K., Weiler, Solly, Gross, Atan, Ashiya, Mona, ...

TNFR1/Fas engagement results in the cleavage of cytosolic BID to truncated tBID, which translocates to mitochondria. Immunodepletion and gene disruption indicate BID is required for cytochrome c...

Phosphorylation of BCL-2 regulates ER Ca2+ homeostasis and apoptosis

Bassik, Michael C, Scorrano, Luca, Oakes, Scott A, Pozzan, Tullio, Korsmeyer, Stanley J

Phosphorylation of BCL-2 within an unstructured loop inhibits its antiapoptotic effect. We found that phosphorylated BCL-2 predominantly localized to the endoplasmic reticulum (ER) and tested whether...

Survival factor-induced extracellular signal-regulated kinase phosphorylates BIM, inhibiting its association with BAX and proapoptotic activity

Harada, Hisashi, Quearry, Bonnie, Ruiz-Vela, Antonio, Korsmeyer, Stanley J.

The “BH3-only” proapoptotic BCL-2 family members initiate the intrinsic apoptotic pathway. A small interfering RNA knockdown of BIM confirms this BH3-only member is important for the...

Proapoptotic BAX and BAK regulate the type 1 inositol trisphosphate receptor and calcium leak from the endoplasmic reticulum

Oakes, Scott A., Scorrano, Luca, Opferman, Joseph T., Bassik, Michael C., Nishino, Mari, Pozzan, Tullio, ...

Proapoptotic BCL-2 family members BAX and BAK are required for the initiation of mitochondrial dysfunction during apoptosis and for maintaining the endoplasmic reticulum (ER) Ca2+ stores necessary...

Conditional MLL-CBP targets GMP and models therapy-related myeloproliferative disease

Wang, Jing, Iwasaki, Hiromi, Krivtsov, Andrei, Febbo, Phillip G, Thorner, Aaron R, Ernst, Patricia, ...

Chromosomal translocations that fuse the mixed lineage leukemia (MLL) gene with multiple partners typify acute leukemias of infancy as well as therapy-related leukemias. We utilized a conditional...

Oligomeric Bax Is a Component of the Putative Cytochrome c Release Channel MAC, Mitochondrial Apoptosis-induced Channel

Dejean, Laurent M., Martinez-Caballero, Sonia, Guo, Liang, Hughes, Cynthia, Teijido, Oscar, Ducret, Thomas, ...

Bcl-2 family proteins regulate apoptosis, in part, by controlling formation of the mitochondrial apoptosis-induced channel (MAC), which is a putative cytochrome c release channel induced early in the...

Essential role of BAX,BAK in B cell homeostasis and prevention of autoimmune disease

Takeuchi, Osamu, Fisher, Jill, Suh, Heikyung, Harada, Hisashi, Malynn, Barbara A., Korsmeyer, Stanley J.

B cell homeostasis is maintained by a balance between the continual generation of new cells and their elimination. Here we show proapoptotic BCL-2 family members BAX and BAK are essential for...

Cyclophilin D is a component of mitochondrial permeability transition and mediates neuronal cell death after focal cerebral ischemia

Schinzel, Anna C., Takeuchi, Osamu, Huang, Zhihong, Fisher, Jill K., Zhou, Zhipeng, Rubens, Jeffery, ...

Mitochondrial permeability transition (PT) is a phenomenon induced by high levels of matrix calcium and is characterized by the opening of the PT pore (PTP). Activation of the PTP results in loss of...

p600, a unique protein required for membrane morphogenesis and cell survival

Nakatani, Yoshihiro, Konishi, Hiroaki, Vassilev, Alex, Kurooka, Hisanori, Ishiguro, Keiichiro, Sawada, Jun-ichi, ...

In this article, we identify and characterize p600, a unique 600-kDa retinoblastoma protein- and calmodulin-binding protein. In the nucleus, p600 and retinoblastoma protein seem to act as a chromatin...

Proapoptotic BAX and BAK control multiple initiator caspases

Ruiz-Vela, Antonio, Opferman, Joseph T, Cheng, Emily H-Y, Korsmeyer, Stanley J

BAX and BAK operate at both the mitochondria and endoplasmic reticulum (ER) to regulate the intrinsic apoptotic pathway. An unresolved issue is whether any caspases can be activated in response to...

Uncleaved TFIIA Is a Substrate for Taspase 1 and Active in Transcription

Zhou, Huiqing, Spicuglia, Salvatore, Hsieh, James J.-D., Mitsiou, Dimitra J., Høiby, Torill, Veenstra, Gert Jan C., ...

In higher eukaryotes, the large subunit of the general transcription factor TFIIA is encoded by the single TFIIAαβ gene and posttranslationally cleaved into α and β subunits. The molecular...

Proteolysis of MLL family proteins is essential for Taspase1-orchestrated cell cycle progression

Takeda, Shugaku, Chen, David Y., Westergard, Todd D., Fisher, Jill K., Rubens, Jeffrey A., Sasagawa, Satoru, ...

Taspase1 was identified as the threonine endopeptidase that cleaves mixed-lineage leukemia (MLL) for proper Hox gene expression in vitro. To investigate its functions in vivo, we generated...

The BCL2A1 gene as a pre–T cell receptor–induced regulator of thymocyte survival

Mandal, Malay, Borowski, Christine, Palomero, Teresa, Ferrando, Adolfo A., Oberdoerffer, Philipp, Meng, Fanyong, ...

The pre–T cell receptor (TCR) is expressed early during T cell development and imposes a tight selection for differentiating T cell progenitors. Pre-TCR–expressing cells are selected to survive...

On the Key Role of Secondary Lymphoid Organs in Antiviral Immune Responses Studied in Alymphoplastic (aly/aly) and Spleenless (Hox11−/−) Mutant Mice

Karrer, Urs, Althage, Alana, Odermatt, Bernhard, Roberts, Charles W.M., Korsmeyer, Stanley J., Miyawaki, Shigeki, ...

The role of the spleen and of other organized secondary lymphoid organs for the induction of protective antiviral immune responses was evaluated in orphan homeobox gene 11 knockout mice...

Regulated Targeting of BAX to Mitochondria

Goping, Ing Swie, Gross, Atan, Lavoie, Josée N., Nguyen, Mai, Jemmerson, Ronald, Roth, Kevin, ...

The proapoptotic protein BAX contains a single predicted transmembrane domain at its COOH terminus. In unstimulated cells, BAX is located in the cytosol and in peripheral association with...

Bax Deletion Further Orders the Cell Death Pathway in Cerebellar Granule Cells and Suggests a Caspase-independent Pathway to Cell Death

Miller, Timothy M., Moulder, Krista L., Knudson, C. Michael, Creedon, Douglas J., Deshmukh, Mohanish, Korsmeyer, Stanley J., ...

Dissociated cerebellar granule cells maintained in medium containing 25 mM potassium undergo an apoptotic death when switched to medium with 5 mM potassium. Granule cells from mice in which Bax, a...

A novel, high conductance channel of mitochondria linked to apoptosis in mammalian cells and Bax expression in yeast

Pavlov, Evgeny V., Priault, Muriel, Pietkiewicz, Dawn, Cheng, Emily H.-Y., Antonsson, Bruno, Manon, Stephen, ...

During apoptosis, proapoptotic factors are released from mitochondria by as yet undefined mechanisms. Patch-clamping of mitochondria and proteoliposomes formed from mitochondrial outer membranes of...

Multiple signaling pathways promote B lymphocyte stimulator–dependent B-cell growth and survival

Woodland, Robert T., Fox, Casey J., Schmidt, Madelyn R., Hammerman, Peter S., Opferman, Joseph T., Korsmeyer, Stanley J., ...

We investigated the mechanism by which B lymphocyte stimulator (BLyS)/BAFF, a tumor necrosis factor superfamily ligand, promotes B-cell survival and resistance to atrophy. BLyS stimulation activates...