Kulkarni, Diptee A., Vazquez, Alexei, Haffty, Bruce G., Bandera, Elisa V., Hu, Wenwei, Sun, Yvonne Y., ...
Murine double minute 4 (MDM4) shares significant structural homology with murine double minute 2 (MDM2) and interacts and regulates transcriptional activity of the tumor suppressor p53. In tumors...
Ramakrishna Ramaswamy, Gyan Bhanot, Jorge Lepre, Gustavo Stolovitzky, Babu Venkataraghavan, Arnold J Levine
One of the major challenges in cancer diagnosis from microarray data is to develop robust classification models which are independent of the analysis techniques used and can combine data from...
Murphy, Eain, Vanicek, Jiri, Robins, Harlan, Shenk, Thomas, Levine, Arnold J.
A quantitative algorithm was developed and applied to predict target genes of microRNAs encoded by herpesviruses. Although there is almost no conservation among microRNAs of different herpesvirus...
Ma, Buyong, Pan, Yongping, Zheng, Jie, Levine, Arnold J., Nussinov, Ruth
The p53 tetramer recognizes specifically a 20-bp DNA element. Here, we examined symmetries encoded in p53 response elements (p53REs). We analyzed base inversion correlations within the half-site, as...
Symmetries in the p53 response-element (p53RE) encode binding modes for p53 tetramer to recognize DNA. We investigated the molecular mechanisms and biological implications of the possible binding...
Coordination and communication between the p53 and IGF-1-AKT-TOR signal transduction pathways (2006)
Levine, Arnold J., Feng, Zhaohui, Mak, Tak W., You, Han, Jin, Shengkan
Over the past 10 years the signal transduction networks for p53, IGF-1-AKT, and TOR pathways have been assembled in worms, flies, and mammals, and their functions elucidated. In the past 1-2 years a...
Overholtzer, Michael, Rao, Pulivarthi H., Favis, Reyna, Lu, Xin-Yan, Elowitz, Michael B., Barany, Francis, ...
The p53 gene is a critical tumor suppressor that is inactivated in a majority of cancers. The central role of p53 in response to stresses such as DNA damage, hypoxia, and oncogene activation...
Jin, Shengkan, Kalkum, Markus, Overholtzer, Michael, Stoffel, Archontoula, Chait, Brian T., Levine, Arnold J.
Jin, Shengkan, Kalkum, Markus, Overholtzer, Michael, Stoffel, Archontoula, Chait, Brian T., Levine, Arnold J.
p53 regulates cell survival by inhibiting PIK3CA in squamous cell carcinomas (2002)
Singh, Bhuvanesh, Reddy, Pabbathi G., Goberdhan, Andy, Walsh, Christine, Dao, Su, Ngai, Ivan, ...
Wrch-1, a novel member of the Rho gene family that is regulated by Wnt-1 (2001)
Tao, Weikang, Pennica, Diane, Xu, Lifeng, Kalejta, Robert F., Levine, Arnold J.
Analysis of p53-regulated gene expression patterns using oligonucleotide arrays (2000)
Zhao, Renbin, Gish, Kurt, Murphy, Maureen, Yin, Yuxin, Notterman, Daniel, Hoffman, William H., ...
Murphy, Maureen, Ahn, Jaimo, Walker, Kristen K., Hoffman, William H., Evans, Ronald M., Levine, Arnold J., ...
Lübbert, Hermann, Hoffman, Beth J., Snutch, Terry P., Van Dyke, Terry, Levine, Arnold J., Hartig, Paul R., ...
We describe a strategy for the cloning of neurotransmitter-receptor and ion-channel cDNAs that is based on electrophysiological assays of mRNA-injected Xenopus oocytes. This procedure circumvents the...
Nucleocytoplasmic shuttling of oncoprotein Hdm2 is required for Hdm2-mediated degradation of p53
Tao, Weikang, Levine, Arnold J.
The Hdm2 oncoprotein inhibits p53 functions by two means: (i) it blocks p53’s transactivation activity and (ii) it targets p53 for degradation in a proteasome-dependent manner. Recent data indicate...
Identification and characterization of a p53 homologue in Drosophila melanogaster
Jin, Shengkan, Martinek, Sebastian, Joo, Woo S., Wortman, Jennifer R., Mirkovic, Nebojsa, Sali, Andrej, ...
The tumor suppressor gene p53 in mammalian cells plays a critical role in safeguarding the integrity of genome. It functions as a sequence-specific transcription factor. Upon activation by a variety...
Generation of oscillations by the p53-Mdm2 feedback loop: A theoretical and experimental study
Maya, Ruth, Segel, Lee A., Alon, Uri, Levine, Arnold J., Oren, Moshe
The intracellular activity of the p53 tumor suppressor protein is regulated through a feedback loop involving its transcriptional target, mdm2. We present a simple mathematical model suggesting that,...
Ruaro, Elisabetta M., Collavin, Licio, Del Sal, Giannino, Haffner, Rebecca, Oren, Moshe, Levine, Arnold J., ...
The involvement of p53 in regulating diverse cellular processes dictates that it must respond to multiple signaling mechanisms, thus coordinating the response to various “stress conditions.”...
P19ARF stabilizes p53 by blocking nucleo-cytoplasmic shuttling of Mdm2
Tao, Weikang, Levine, Arnold J.
The INK4a-ARF locus encodes two distinct tumor suppressors, p16INK4a and p19ARF. Whereas p16INK4a restrains cell growth through preventing phosphorylation of the retinoblastoma protein, p19ARF acts...
Non-p53 p53RE binding protein, a human transcription factor functionally analogous to P53
Zeng, Xiaoya, Levine, Arnold J., Lu, Hua
The transactivation activity of the p53 tumor suppressor protein is critical for regulating cell growth and apoptosis. We describe the identification of a transcription factor that is functionally...
Pennica, Diane, Swanson, Todd A., Welsh, James W., Roy, Margaret A., Lawrence, David A., Lee, James, ...
Wnt family members are critical to many developmental processes, and components of the Wnt signaling pathway have been linked to tumorigenesis in familial and sporadic colon carcinomas. Here we...
A male germ cell tumor-susceptibility-determining locus, pgct1, identified on murine chromosome 13
Muller, Alexander J., Teresky, Angelika K., Levine, Arnold J.
Inbred 129 strain mice are predisposed to developing male germ cell tumors (GCTs) of the testes. The inherent genetic defects that underlie male GCT susceptibility in the 129 mouse strain are...
Lu, Hua, Taya, Yoichi, Ikeda, Masako, Levine, Arnold J.
Polyclonal antibodies were produced and purified that selectively react with a p53 epitope containing the murine phosphoserine-389 or the human phosphoserine-392 residue, but not the unphosphorylated...
Ziemer, Lisa Taneyhill, Pennica, Diane, Levine, Arnold J.
The Wnt/Wg signaling pathway functions during development to regulate cell fate determination and patterning in various organisms. Two pathways are reported to lie downstream of Wnt signaling in...
Nuclear Export Is Required for Degradation of Endogenous p53 by MDM2 and Human Papillomavirus E6
Freedman, Deborah A., Levine, Arnold J.
The MDM2 oncoprotein targets the p53 tumor suppressor protein for degradation when the two proteins are expressed in cells. The regulation of p53 levels by MDM2 requires the ability of MDM2 to be...
Schell, Todd D., Mylin, Lawrence M., Georgoff, Ingo, Teresky, Angelica K., Levine, Arnold J., Tevethia, Satvir S.
The simian virus 40 (SV40) large tumor antigen (Tag) is a virus-encoded oncoprotein which is the target of a strong cytotoxic T-lymphocyte (CTL) response. Three immunodominant H-2b-restricted...
Casau, Armelle E., Vaughan, Joe E., Lozano, Guillermina, Levine, Arnold J.
In contrast to most other human endogenous retroviral families, various HERV-K members have open reading frames that code for functional viral proteins which can form noninfectious particles in some...
p53 regulates cell survival by inhibiting PIK3CA in squamous cell carcinomas
Singh, Bhuvanesh, Reddy, Pabbathi G., Goberdhan, Andy, Walsh, Christine, Dao, Su, Ngai, Ivan, ...
Interactions between the p53 and PI3K/AKT pathways play a significant role in the determination of cell death/survival. In benign cells these pathways are interrelated through the transcriptional...
Jin, Shengkan, Kalkum, Markus, Overholtzer, Michael, Stoffel, Archontoula, Chait, Brian T., Levine, Arnold J.
Recently a Drosophila p53 protein has been identified that mediates apoptosis via a novel pathway involving the activation of the Reaper gene and subsequent inhibition of the inhibitors of apoptosis...
Overholtzer, Michael, Rao, Pulivarthi H., Favis, Reyna, Lu, Xin-Yan, Elowitz, Michael B., Barany, Francis, ...
The p53 gene is a critical tumor suppressor that is inactivated in a majority of cancers. The central role of p53 in response to stresses such as DNA damage, hypoxia, and oncogene activation...
ISOLATION OF A CHLORAMPHENICOL-RESISTANT PROTEIN FROM λ-INFECTED CELLS*
Levine, Arnold J., Sinsheimer, Robert L.
During infection with bacteriophage ϕX174, a protein, made in the presence of 30 γ chloramphenicol/ml but not made in the presence of concentrations greater than 100 γ/ml, has been shown to be...
Yue, Zhenyu, Jin, Shengkan, Yang, Chingwen, Levine, Arnold J., Heintz, Nathaniel
The biochemical properties of beclin 1 suggest a role in two fundamentally important cell biological pathways: autophagy and apoptosis. We show here that beclin 1-/- mutant mice die early in...
WISP-1 is a Wnt-1- and β-catenin-responsive oncogene
Xu, Lifeng, Corcoran, Ryan B., Welsh, James W., Pennica, Diane, Levine, Arnold J.
WISP-1 (Wnt-1 induced secreted protein 1) is a member of the CCN family of growth factors. This study identifies WISP-1 as a β-catenin-regulated gene that can contribute to tumorigenesis. The...
Analysis of p53-regulated gene expression patterns using oligonucleotide arrays
Zhao, Renbin, Gish, Kurt, Murphy, Maureen, Yin, Yuxin, Notterman, Daniel, Hoffman, William H., ...
Oligonucleotide microarrays were employed to quantitate mRNA levels from a large number of genes regulated by the p53 transcription factor. Responses to DNA damage and to zinc-inducible p53 were...
Murphy, Maureen, Ahn, Jaimo, Walker, Kristen K., Hoffman, William H., Evans, Ronald M., Levine, Arnold J., ...
There is growing evidence that the p53 tumor suppressor protein not only can function to activate gene transcription but also to repress the expression of specific genes. Although recent studies have...
Fox, Thomas O., Levine, Arnold J.
The fraction of cells in a confluent 3T3 cell monolayer induced by simian virus 40 infection to replicate deoxyribonucleic acid and divide corresponds to those cells which eventually become...
Dubbs, Del Rose, Kit, Saul, Jaenisch, Rudolf, Levine, Arnold J.
Oligomeric forms of simian virus 40 (SV40) deoxyribonucleic acid (DNA) were isolated from monkey kidney cells infected with two plaque morphology mutants of SV40. Recombinant, large clear-plaque-type...
Levine, Arnold J., Teresky, Angelika K.
Purified simian virus 40 (SV40) virions, grown in primary African green monkey kidney cells labeled prior to infection with 3H-thymidine, contain a variable quantity of 3H-labeled deoxyribonucleic...
Ritzi, Earl, Levine, Arnold J.
A comparative study of simian virus 40 (SV40) lytic infection in three different monkey cell lines is described. The results demonstrate that viral deoxyribonucleic acid (DNA) synthesis and...
Infection of confluent monolayer cultures of African green monkey kidney cells with simian virus 40 results in an enhanced synthesis of nuclear and mitochondrial DNA. This is demonstrated both by an...
Stoffel, Archontoula, Chaurushiya, Mira, Singh, Bhuvanesh, Levine, Arnold J.
Mucosa-associated lymphoid tissue (MALT) lymphoma is the most common extranodal lymphoid cell neoplasia; it frequently follows chronic bacteria-induced inflammation in various tissues. MALT lymphomas...
Tissue-specific codon usage and the expression of human genes
Plotkin, Joshua B., Robins, Harlan, Levine, Arnold J.
A diverse array of mechanisms regulate tissue-specific protein levels. Most research, however, has focused on the role of transcriptional regulation. Here we report systematic differences in...
Ma, Buyong, Pan, Yongping, Gunasekaran, K., Venkataraghavan, R. Babu, Levine, Arnold J., Nussinov, Ruth
p53, the tumor suppressor protein, functions as a dimer of dimers. However, how the tetramer binds to the DNA is still an open question. In the crystal structure, three copies of the p53 monomers...
The coordinate regulation of the p53 and mTOR pathways in cells
Feng, Zhaohui, Zhang, Haiyan, Levine, Arnold J., Jin, Shengkan
Cell growth and proliferation requires an intricate coordination between the stimulatory signals arising from nutrients and growth factors and the inhibitory signals arising from intracellular and...
A Relative-Entropy Algorithm for Genomic Fingerprinting Captures Host-Phage Similarities
Robins, Harlan, Krasnitz, Michael, Barak, Hagar, Levine, Arnold J.
The degeneracy of codons allows a multitude of possible sequences to code for the same protein. Hidden within the particular choice of sequence for each organism are over 100 previously undiscovered...
Wrch-1, a novel member of the Rho gene family that is regulated by Wnt-1
Tao, Weikang, Pennica, Diane, Xu, Lifeng, Kalejta, Robert F., Levine, Arnold J.
We report the isolation and cloning of the Wrch-1 (Wnt-1 responsive Cdc42 homolog) cDNA. Wrch-1 is a novel gene whose mRNA level increases in response to Wnt-1 signaling in Wnt-1 transformed cells,...
A plausible model for the digital response of p53 to DNA damage
Ma, Lan, Wagner, John, Rice, John Jeremy, Hu, Wenwei, Levine, Arnold J., Stolovitzky, Gustavo A.
Recent observations show that the single-cell response of p53 to ionizing radiation (IR) is “digital” in that it is the number of oscillations rather than the amplitude of p53 that shows...
Su, Fei, Overholtzer, Michael, Besser, Daniel, Levine, Arnold J.
WISP-1 (Wnt-1-induced secreted protein) was identified as an oncogene regulated by the Wnt-1–β-catenin pathway. WISP-1 belongs to the CCN family of growth factors, which are cysteine-rich,...
Detection of functional single-nucleotide polymorphisms that affect apoptosis
Harris, Sandra L., Gil, German, Robins, Harlan, Hu, Wenwei, Hirshfield, Kim, Bond, Elisabeth, ...
Human EBV-transformed B lymphocyte cell lines (LCLs) were used to measure the apoptotic response of individuals to γ radiation. The responses form a normal distribution around a median of 35.5%...
Nucleocytoplasmic shuttling of oncoprotein Hdm2 is required for Hdm2-mediated degradation of p53
Tao, Weikang, Levine, Arnold J.
The Hdm2 oncoprotein inhibits p53 functions by two means: (i) it blocks p53’s transactivation activity and (ii) it targets p53 for degradation in a proteasome-dependent manner. Recent data indicate...
Identification and characterization of a p53 homologue in Drosophila melanogaster
Jin, Shengkan, Martinek, Sebastian, Joo, Woo S., Wortman, Jennifer R., Mirkovic, Nebojsa, Sali, Andrej, ...
The tumor suppressor gene p53 in mammalian cells plays a critical role in safeguarding the integrity of genome. It functions as a sequence-specific transcription factor. Upon activation by a variety...
Generation of oscillations by the p53-Mdm2 feedback loop: A theoretical and experimental study
Maya, Ruth, Segel, Lee A., Alon, Uri, Levine, Arnold J., Oren, Moshe
The intracellular activity of the p53 tumor suppressor protein is regulated through a feedback loop involving its transcriptional target, mdm2. We present a simple mathematical model suggesting that,...
Ruaro, Elisabetta M., Collavin, Licio, Del Sal, Giannino, Haffner, Rebecca, Oren, Moshe, Levine, Arnold J., ...
The involvement of p53 in regulating diverse cellular processes dictates that it must respond to multiple signaling mechanisms, thus coordinating the response to various “stress conditions.”...
P19ARF stabilizes p53 by blocking nucleo-cytoplasmic shuttling of Mdm2
Tao, Weikang, Levine, Arnold J.
The INK4a-ARF locus encodes two distinct tumor suppressors, p16INK4a and p19ARF. Whereas p16INK4a restrains cell growth through preventing phosphorylation of the retinoblastoma protein, p19ARF acts...
Non-p53 p53RE binding protein, a human transcription factor functionally analogous to P53
Zeng, Xiaoya, Levine, Arnold J., Lu, Hua
The transactivation activity of the p53 tumor suppressor protein is critical for regulating cell growth and apoptosis. We describe the identification of a transcription factor that is functionally...
Pennica, Diane, Swanson, Todd A., Welsh, James W., Roy, Margaret A., Lawrence, David A., Lee, James, ...
Wnt family members are critical to many developmental processes, and components of the Wnt signaling pathway have been linked to tumorigenesis in familial and sporadic colon carcinomas. Here we...
A male germ cell tumor-susceptibility-determining locus, pgct1, identified on murine chromosome 13
Muller, Alexander J., Teresky, Angelika K., Levine, Arnold J.
Inbred 129 strain mice are predisposed to developing male germ cell tumors (GCTs) of the testes. The inherent genetic defects that underlie male GCT susceptibility in the 129 mouse strain are...
Lu, Hua, Taya, Yoichi, Ikeda, Masako, Levine, Arnold J.
Polyclonal antibodies were produced and purified that selectively react with a p53 epitope containing the murine phosphoserine-389 or the human phosphoserine-392 residue, but not the unphosphorylated...
Ziemer, Lisa Taneyhill, Pennica, Diane, Levine, Arnold J.
The Wnt/Wg signaling pathway functions during development to regulate cell fate determination and patterning in various organisms. Two pathways are reported to lie downstream of Wnt signaling in...
Nuclear Export Is Required for Degradation of Endogenous p53 by MDM2 and Human Papillomavirus E6
Freedman, Deborah A., Levine, Arnold J.
The MDM2 oncoprotein targets the p53 tumor suppressor protein for degradation when the two proteins are expressed in cells. The regulation of p53 levels by MDM2 requires the ability of MDM2 to be...
Schell, Todd D., Mylin, Lawrence M., Georgoff, Ingo, Teresky, Angelica K., Levine, Arnold J., Tevethia, Satvir S.
The simian virus 40 (SV40) large tumor antigen (Tag) is a virus-encoded oncoprotein which is the target of a strong cytotoxic T-lymphocyte (CTL) response. Three immunodominant H-2b-restricted...
Casau, Armelle E., Vaughan, Joe E., Lozano, Guillermina, Levine, Arnold J.
In contrast to most other human endogenous retroviral families, various HERV-K members have open reading frames that code for functional viral proteins which can form noninfectious particles in some...
p53 regulates cell survival by inhibiting PIK3CA in squamous cell carcinomas
Singh, Bhuvanesh, Reddy, Pabbathi G., Goberdhan, Andy, Walsh, Christine, Dao, Su, Ngai, Ivan, ...
Interactions between the p53 and PI3K/AKT pathways play a significant role in the determination of cell death/survival. In benign cells these pathways are interrelated through the transcriptional...
Su, Fei, Overholtzer, Michael, Besser, Daniel, Levine, Arnold J.
WISP-1 (Wnt-1-induced secreted protein) was identified as an oncogene regulated by the Wnt-1–β-catenin pathway. WISP-1 belongs to the CCN family of growth factors, which are cysteine-rich,...
Jin, Shengkan, Kalkum, Markus, Overholtzer, Michael, Stoffel, Archontoula, Chait, Brian T., Levine, Arnold J.
Recently a Drosophila p53 protein has been identified that mediates apoptosis via a novel pathway involving the activation of the Reaper gene and subsequent inhibition of the inhibitors of apoptosis...
Overholtzer, Michael, Rao, Pulivarthi H., Favis, Reyna, Lu, Xin-Yan, Elowitz, Michael B., Barany, Francis, ...
The p53 gene is a critical tumor suppressor that is inactivated in a majority of cancers. The central role of p53 in response to stresses such as DNA damage, hypoxia, and oncogene activation...
ISOLATION OF A CHLORAMPHENICOL-RESISTANT PROTEIN FROM λ-INFECTED CELLS*
Levine, Arnold J., Sinsheimer, Robert L.
During infection with bacteriophage ϕX174, a protein, made in the presence of 30 γ chloramphenicol/ml but not made in the presence of concentrations greater than 100 γ/ml, has been shown to be...
Yue, Zhenyu, Jin, Shengkan, Yang, Chingwen, Levine, Arnold J., Heintz, Nathaniel
The biochemical properties of beclin 1 suggest a role in two fundamentally important cell biological pathways: autophagy and apoptosis. We show here that beclin 1-/- mutant mice die early in...
Wrch-1, a novel member of the Rho gene family that is regulated by Wnt-1
Tao, Weikang, Pennica, Diane, Xu, Lifeng, Kalejta, Robert F., Levine, Arnold J.
We report the isolation and cloning of the Wrch-1 (Wnt-1 responsive Cdc42 homolog) cDNA. Wrch-1 is a novel gene whose mRNA level increases in response to Wnt-1 signaling in Wnt-1 transformed cells,...
WISP-1 is a Wnt-1- and β-catenin-responsive oncogene
Xu, Lifeng, Corcoran, Ryan B., Welsh, James W., Pennica, Diane, Levine, Arnold J.
WISP-1 (Wnt-1 induced secreted protein 1) is a member of the CCN family of growth factors. This study identifies WISP-1 as a β-catenin-regulated gene that can contribute to tumorigenesis. The...
Analysis of p53-regulated gene expression patterns using oligonucleotide arrays
Zhao, Renbin, Gish, Kurt, Murphy, Maureen, Yin, Yuxin, Notterman, Daniel, Hoffman, William H., ...
Oligonucleotide microarrays were employed to quantitate mRNA levels from a large number of genes regulated by the p53 transcription factor. Responses to DNA damage and to zinc-inducible p53 were...
Murphy, Maureen, Ahn, Jaimo, Walker, Kristen K., Hoffman, William H., Evans, Ronald M., Levine, Arnold J., ...
There is growing evidence that the p53 tumor suppressor protein not only can function to activate gene transcription but also to repress the expression of specific genes. Although recent studies have...
Fox, Thomas O., Levine, Arnold J.
The fraction of cells in a confluent 3T3 cell monolayer induced by simian virus 40 infection to replicate deoxyribonucleic acid and divide corresponds to those cells which eventually become...
Dubbs, Del Rose, Kit, Saul, Jaenisch, Rudolf, Levine, Arnold J.
Oligomeric forms of simian virus 40 (SV40) deoxyribonucleic acid (DNA) were isolated from monkey kidney cells infected with two plaque morphology mutants of SV40. Recombinant, large clear-plaque-type...
Levine, Arnold J., Teresky, Angelika K.
Purified simian virus 40 (SV40) virions, grown in primary African green monkey kidney cells labeled prior to infection with 3H-thymidine, contain a variable quantity of 3H-labeled deoxyribonucleic...
Ritzi, Earl, Levine, Arnold J.
A comparative study of simian virus 40 (SV40) lytic infection in three different monkey cell lines is described. The results demonstrate that viral deoxyribonucleic acid (DNA) synthesis and...
Infection of confluent monolayer cultures of African green monkey kidney cells with simian virus 40 results in an enhanced synthesis of nuclear and mitochondrial DNA. This is demonstrated both by an...
Stoffel, Archontoula, Chaurushiya, Mira, Singh, Bhuvanesh, Levine, Arnold J.
Mucosa-associated lymphoid tissue (MALT) lymphoma is the most common extranodal lymphoid cell neoplasia; it frequently follows chronic bacteria-induced inflammation in various tissues. MALT lymphomas...
Tissue-specific codon usage and the expression of human genes
Plotkin, Joshua B., Robins, Harlan, Levine, Arnold J.
A diverse array of mechanisms regulate tissue-specific protein levels. Most research, however, has focused on the role of transcriptional regulation. Here we report systematic differences in...
Ma, Buyong, Pan, Yongping, Gunasekaran, K., Venkataraghavan, R. Babu, Levine, Arnold J., Nussinov, Ruth
p53, the tumor suppressor protein, functions as a dimer of dimers. However, how the tetramer binds to the DNA is still an open question. In the crystal structure, three copies of the p53 monomers...
The coordinate regulation of the p53 and mTOR pathways in cells
Feng, Zhaohui, Zhang, Haiyan, Levine, Arnold J., Jin, Shengkan
Cell growth and proliferation requires an intricate coordination between the stimulatory signals arising from nutrients and growth factors and the inhibitory signals arising from intracellular and...
A plausible model for the digital response of p53 to DNA damage
Ma, Lan, Wagner, John, Rice, John Jeremy, Hu, Wenwei, Levine, Arnold J., Stolovitzky, Gustavo A.
Recent observations show that the single-cell response of p53 to ionizing radiation (IR) is “digital” in that it is the number of oscillations rather than the amplitude of p53 that shows...
Detection of functional single-nucleotide polymorphisms that affect apoptosis
Harris, Sandra L., Gil, German, Robins, Harlan, Hu, Wenwei, Hirshfield, Kim, Bond, Elisabeth, ...
Human EBV-transformed B lymphocyte cell lines (LCLs) were used to measure the apoptotic response of individuals to γ radiation. The responses form a normal distribution around a median of 35.5%...
A Relative-Entropy Algorithm for Genomic Fingerprinting Captures Host-Phage Similarities
Robins, Harlan, Krasnitz, Michael, Barak, Hagar, Levine, Arnold J.
The degeneracy of codons allows a multitude of possible sequences to code for the same protein. Hidden within the particular choice of sequence for each organism are over 100 previously undiscovered...
Comparison of Avian and Human Influenza A Viruses Reveals a Mutational Bias on the Viral Genomes▿
Rabadan, Raul, Levine, Arnold J., Robins, Harlan
In the last few years, the genomic sequence data for thousands of influenza A virus strains, including the 1918 pandemic strain, and hundreds of isolates of the avian influenza virus H5N1, which is...
Ma, Buyong, Pan, Yongping, Zheng, Jie, Levine, Arnold J., Nussinov, Ruth
The p53 tetramer recognizes specifically a 20-bp DNA element. Here, we examined symmetries encoded in p53 response elements (p53REs). We analyzed base inversion correlations within the half-site, as...
Haplotype structure and selection of the MDM2 oncogene in humans
Atwal, Gurinder Singh, Bond, Gareth L., Metsuyanim, Sally, Papa, Moshe, Friedman, Eitan, Distelman-Menachem, Tal, ...
The MDM2 protein is an ubiquitin ligase that plays a critical role in regulating the levels and activity of the p53 protein, which is a central tumor suppressor. A SNP in the human MDM2 gene (SNP309...
Symmetries in the p53 response-element (p53RE) encode binding modes for p53 tetramer to recognize DNA. We investigated the molecular mechanisms and biological implications of the possible binding...
An Information-Theoretic Analysis of Genetics, Gender and Age in Cancer Patients
Atwal, Gurinder Singh, Rabadán, Raúl, Lozano, Guillermina, Strong, Louise C., Ruijs, Mariëlle W. G., Schmidt, Marjanka K., ...
Germline genetics, gender and hormonal-signaling pathways are all well described modifiers of cancer risk and progression. Although an improved understanding of how germline genetic variants interact...
Feng, Zhaohui, Hu, Wenwei, Teresky, Angelika K., Hernando, Eva, Cordon-Cardo, Carlos, Levine, Arnold J.
Cancer is a disease of aging. The accumulation of mutations in individual cells over a lifetime is thought to be the reason. In this work, we explored an additional hypothesis: could p53 function...
Theobald, Matthias, Ruppert, Thomas, Kuckelkorn, Ulrike, Hernandez, Javier, Häussler, Annett, Ferreira, Edite Antunes, ...
A high proportion of tumors arise due to mutation of the p53 tumor suppressor protein. A p53 hotspot mutation at amino acid position 273 from R to H, flanking a peptide epitope that spans residues...
Patterns of Evolution and Host Gene Mimicry in Influenza and Other RNA Viruses
Greenbaum, Benjamin D., Levine, Arnold J., Bhanot, Gyan, Rabadan, Raul
It is well known that the dinucleotide CpG is under-represented in the genomic DNA of many vertebrates. This is commonly thought to be due to the methylation of cytosine residues in this dinucleotide...
Marsh, Glenn A., Rabadán, Raúl, Levine, Arnold J., Palese, Peter
The genome of the influenza A virus is composed of eight different segments of negative-sense RNA. These eight segments are incorporated into budding virions in an equimolar ratio through a mechanism...
A Recoding Method to Improve the Humoral Immune Response to an HIV DNA Vaccine
Huang, Yaoxing, Krasnitz, Michael, Rabadan, Raul, Witten, Daniela M., Song, Yang, Levine, Arnold J., ...
This manuscript describes a novel strategy to improve HIV DNA vaccine design. Employing a new information theory based bioinformatic algorithm, we identify a set of nucleotide motifs which are common...
Murphy, Eain, Vaníček, Jiří, Robins, Harlan, Shenk, Thomas, Levine, Arnold J.
A quantitative algorithm was developed and applied to predict target genes of microRNAs encoded by herpesviruses. Although there is almost no conservation among microRNAs of different herpesvirus...
Anomalies in the Influenza Virus Genome Database: New Biology or Laboratory Errors?▿ †
Krasnitz, Michael, Levine, Arnold J., Rabadan, Raul
A search of the influenza virus genome database reveals anomalies associated with a nonnegligible number of submitted sequences. There are many pairs of viral segments that are very close to each...
Greenbaum, Benjamin D., Rabadan, Raul, Levine, Arnold J.
The innate immune response provides a first line of defense against pathogens by targeting generic differential features that are present in foreign organisms but not in the host. These innate...
Altered tumor formation and evolutionary selection of genetic variants in the human MDM4 oncogene
Atwal, Gurinder Singh, Kirchhoff, Tomas, Bond, Elisabeth E., Montagna, Marco, Menin, Chiara, Bertorelle, Roberta, ...
A large body of evidence strongly suggests that the p53 tumor suppressor pathway is central in reducing cancer frequency in vertebrates. The protein product of the haploinsufficient mouse double...