Showing 1-26 of 26 results for "

MABE281

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Muktar A Mahajan et al.
Molecular endocrinology (Baltimore, Md.), 21(8), 1822-1834 (2007-05-31)
Nuclear receptor coregulator (NRC) is a 250-kDa nuclear protein involved in transcriptional activation of nuclear hormone receptors, nuclear factor-kappaB, c-Jun, c-Fos, and cAMP response element-binding protein. NRC is organized into a modular structure consisting of two activation domains (AD1 and...
Chui Chui Ho et al.
Cancer research, 66(4), 2233-2241 (2006-02-21)
Stalled replication forks induce p53, which is required to maintain the replication checkpoint. In contrast to the well-established mechanisms of DNA damage-activated p53, the downstream effectors and upstream regulators of p53 during replication blockade remain to be deciphered. Hydroxyurea triggered...
J-L Roh et al.
Cell death & disease, 4, e956-e956 (2013-12-18)
The tumor suppressor p53 is often inactivated in head and neck cancer (HNC) through TP53 mutations or overexpression of mouse double minute 2 or mouse double minute X. Restoration of p53 function by counteracting these p53 repressors is a promising...
L Davies et al.
Cell death & disease, 2, e136-e136 (2011-04-01)
The activation and regulation of target genes by the tumour-suppressor p53 dictates the fate of a cell, with cell cycle arrest or apoptosis being two distinct outcomes. PERP (p53 apoptosis effector related to PMP-22), a p53 transcriptional target, is induced...
Saeed Arefanian et al.
Oncoimmunology, 5(12), e1238543-e1238543 (2017-01-27)
Individuals with robust natural killer (NK) cell function incur lower rates of malignancies. To expand our understanding of genetic factors contributing to this phenomenon, we analyzed NK cells from cancer resistant and susceptible strains of mice. We identified a correlation...
Giusy Di Conza et al.
Cell cycle (Georgetown, Tex.), 11(4), 749-760 (2012-03-01)
Stabilization of p53 protein is an important step in the activation of its function. p53 levels are regulated by ubiquitin-dependent and -independent degradation pathways. MDM4 (MDMX) is an important regulator of p53, able to both stimulate and antagonize p53 degradation....
Akinori Morita et al.
Cancer research, 70(1), 257-265 (2010-01-06)
Sodium orthovanadate (vanadate) inhibits the DNA-binding activity of p53, but its precise effects on p53 function have not been examined. Here, we show that vanadate exerts a potent antiapoptotic activity through both transcription-dependent and transcription-independent mechanisms relative to other p53...
Susie Lee et al.
PloS one, 5(6), e10995-e10995 (2010-06-12)
Cell proliferation in all rapidly renewing mammalian tissues follows a circadian rhythm that is often disrupted in advanced-stage tumors. Epidemiologic studies have revealed a clear link between disruption of circadian rhythms and cancer development in humans. Mice lacking the circadian...
Jong-Hee Lee et al.
The Journal of biological chemistry, 283(28), 19826-19835 (2008-05-21)
The p53 tumor suppressor protein, a critical modulator of cellular stress responses, is activated through diverse mechanisms that result in its stabilization and transcriptional activation. p53 activity is controlled by transcriptional, translational, and post-translational regulation. The major mechanisms of p53...
Manabu Kurokawa et al.
Science signaling, 6(274), ra32-ra32 (2013-05-09)
In the intrinsic pathway of apoptosis, cell-damaging signals promote the release of cytochrome c from mitochondria, triggering activation of the Apaf-1 and caspase-9 apoptosome. The ubiquitin E3 ligase MDM2 decreases the stability of the proapoptotic factor p53. We show that...
Francesca Mancini et al.
The EMBO journal, 28(13), 1926-1939 (2009-06-13)
MDM4 is a key regulator of p53, whose biological activities depend on both transcriptional activity and transcription-independent mitochondrial functions. MDM4 binds to p53 and blocks its transcriptional activity; however, the main cytoplasmic localization of MDM4 might also imply a regulation...
Lixian Oh et al.
BMC cancer, 20(1), 110-110 (2020-02-12)
TP53 mutations occur in only about 3% of primary and 10-20% of relapse B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). However, alternative mechanisms may contribute to functionally impairing the p53 pathway in the absence of a mutation. Candidate mechanisms include overexpression...
Connie Chao et al.
Molecular and cellular biology, 26(18), 6859-6869 (2006-09-01)
Posttranslational modifications of p53, including phosphorylation and acetylation, play important roles in regulating p53 stability and activity. Mouse p53 is acetylated at lysine 317 by PCAF and at multiple lysine residues at the extreme carboxyl terminus by CBP/p300 in response...
Andrés Pizzorno et al.
Scientific reports, 8(1), 3746-3746 (2018-03-01)
The interplay between influenza A viruses (IAV) and the p53 pathway has been reported in several studies, highlighting the antiviral contribution of p53. Here, we investigated the impact of IAV on the E3-ubiquitin ligase Mdm2, a major regulator of p53...
Giuseppe Arena et al.
Molecular cell, 69(4), 594-609 (2018-02-18)
Accumulating evidence indicates that the MDM2 oncoprotein promotes tumorigenesis beyond its canonical negative effects on the p53 tumor suppressor, but these p53-independent functions remain poorly understood. Here, we show that a fraction of endogenous MDM2 is actively imported in mitochondria...
Jeffrey R Skaar et al.
Molecular and cellular biology, 25(13), 5579-5589 (2005-06-21)
CUL7, a recently identified member of the cullin family of E3 ubiquitin ligases, forms a unique SCF-like complex and is required for mouse embryonic development. To further investigate CUL7 function, we sought to identify CUL7 binding proteins. The p53-associated, parkin-like...
Sean M Post et al.
Cancer cell, 18(3), 220-230 (2010-09-14)
MDM2, a negative regulator of p53, is elevated in many cancers that retain wild-type p53. A single nucleotide polymorphism (SNP) in the human MDM2 promoter increases the affinity of Sp1 resulting in elevated MDM2 levels. We generated mice carrying either...
V Gama et al.
Cell death and differentiation, 16(5), 758-769 (2009-02-28)
Earlier, we have reported that 70 kDa subunit of Ku protein heterodimer (Ku70) binds and inhibits Bax activity in the cytosol and that ubiquitin (Ub)-dependent proteolysis of cytosolic Ku70 facilitates Bax-mediated apoptosis. We found that Hdm2 (human homolog of murine...
Oliver Bischof et al.
Molecular cell, 22(6), 783-794 (2006-06-24)
Cellular senescence and apoptosis have evolved to restrain unwarranted proliferation of potentially tumorigenic cells. Here we show that overexpression of the E3 SUMO ligase PIASy in normal human fibroblasts recruits the p53 and Rb tumor suppressor pathways to provoke a...
Kyle P Feeley et al.
Cancer research, 77(14), 3823-3833 (2017-06-04)
p53 deletion prevents the embryonic lethality of normal tissues lacking Mdm2, suggesting that cells can survive without Mdm2 if p53 is also absent. Here we report evidence challenging this view, with implications for therapeutically targeting Mdm2. Deletion of Mdm2 in...
Elisabeth Silden et al.
PloS one, 8(2), e56276-e56276 (2013-02-15)
The carboxy-terminal truncated p53 alternative spliced isoforms, p53β and p53γ, are expressed at disparate levels in cancer and are suggested to influence treatment response and therapy outcome. However, their functional role in cancer remains to be elucidated. We investigated their...
Batzaya Davaadelger et al.
PloS one, 9(11), e110844-e110844 (2014-11-08)
Tetraploid (4N) cells are considered important in cancer because they can display increased tumorigenicity, resistance to conventional therapies, and are believed to be precursors to whole chromosome aneuploidy. It is therefore important to determine how tetraploid cancer cells arise, and...
Shunbin Xiong et al.
Cancer research, 70(18), 7148-7154 (2010-08-26)
High levels of the critical p53 inhibitor Mdm4 is common in tumors that retain a wild-type p53 allele, suggesting that Mdm4 overexpression is an important mechanism for p53 inactivation during tumorigenesis. To test this hypothesis in vivo, we generated transgenic...
P Erhardt et al.
The Journal of biological chemistry, 272(24), 15049-15052 (1997-06-13)
Programmed cell death is mediated by members of the interleukin 1-beta convertase family of proteases, which are activated in response to diverse cell death stimuli. However, the key substrates of these proteases that are responsible for apoptotic cell death have...
Xiang Gao et al.
International journal of molecular sciences, 21(13) (2020-07-08)
3,3'-Diindolylmethane (DIM) is a naturally derived chemopreventive compound. It comes from glucobrassicin, an indole glucosinolate enriched in cruciferous vegetables, and is formed in the acidic environment of the stomach after ingestion. Mouse double minute 2 homolog (MDM2) is an important...
Vinod Pant et al.
Genes & development, 27(17), 1857-1867 (2013-08-27)
The p53-Mdm2 feedback loop is perceived to be critical for regulating stress-induced p53 activity and levels. However, this has never been tested in vivo. Using a genetically engineered mouse with mutated p53 response elements in the Mdm2 P2 promoter, we...