scholarly journals PKR is not a universal target of tumor suppressor p53 in response to genotoxic stress

Cell Cycle ◽  
2009 ◽  
Vol 8 (21) ◽  
pp. 3606-3607 ◽  
Author(s):  
Mashrur Rahman ◽  
Christopher Lem ◽  
Hala Muaddi ◽  
Antonis Koromilas
Keyword(s):  
Tumor Suppressor ◽  
Genotoxic Stress ◽  
Tumor Suppressor P53

scholarly journals The Tumor Suppressor p53 and Histone Deacetylase 1 Are Antagonistic Regulators of the Cyclin-Dependent Kinase Inhibitor p21/WAF1/CIP1 Gene

2003 ◽  
Vol 23 (8) ◽  
pp. 2669-2679 ◽  
Author(s):  
Gerda Lagger ◽  
Angelika Doetzlhofer ◽  
Bernd Schuettengruber ◽  
Eva Haidweger ◽  
Elisabeth Simboeck ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Histone Deacetylase ◽  
Kinase Inhibitor ◽  
Genotoxic Stress ◽  
Cyclin Dependent Kinase ◽  
Tumor Suppressor P53 ◽  
Histone Deacetylase 1 ◽  
Cyclin Dependent Kinase Inhibitor ◽  
C Terminus ◽  
P21 Promoter

ABSTRACT The cyclin-dependent kinase inhibitor p21/WAF1/CIP1 is an important regulator of cell cycle progression, senescence, and differentiation. Genotoxic stress leads to activation of the tumor suppressor p53 and subsequently to induction of p21 expression. Here we show that the tumor suppressor p53 cooperates with the transcription factor Sp1 in the activation of the p21 promoter, whereas histone deacetylase 1 (HDAC1) counteracts p53-induced transcription from the p21 gene. The p53 protein binds directly to the C terminus of Sp1, a domain which was previously shown to be required for the interaction with HDAC1. Induction of p53 in response to DNA-damaging agents resulted in the formation of p53-Sp1 complexes and simultaneous dissociation of HDAC1 from the C terminus of Sp1. Chromatin immunoprecipitation experiments demonstrated the association of HDAC1 with the p21 gene in proliferating cells. Genotoxic stress led to recruitment of p53, reduced binding of HDAC1, and hyperacetylation of core histones at the p21 promoter. Our findings show that the deacetylase HDAC1 acts as an antagonist of the tumor suppressor p53 in the regulation of the cyclin-dependent kinase inhibitor p21 and provide a basis for understanding the function of histone deacetylase inhibitors as antitumor drugs.

scholarly journals Regulators of Oncogenic Mutant TP53 Gain of Function

Cancers ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 4 ◽  
Author(s):  
Satomi Yamamoto ◽  
Tomoo Iwakuma
Keyword(s):  
Tumor Suppressor ◽  
Gene Mutations ◽  
Genotoxic Stress ◽  
Tumor Suppressor P53 ◽  
Tumor Suppressor Function ◽  
Wild Type ◽  
Nucleotide Polymorphism ◽  
Gain Of Function ◽  
Single Nucleotide ◽  
Post Translational Modifications

The tumor suppressor p53 (TP53) is the most frequently mutated human gene. Mutations in TP53 not only disrupt its tumor suppressor function, but also endow oncogenic gain-of-function (GOF) activities in a manner independent of wild-type TP53 (wtp53). Mutant TP53 (mutp53) GOF is mainly mediated by its binding with other tumor suppressive or oncogenic proteins. Increasing evidence indicates that stabilization of mutp53 is crucial for its GOF activity. However, little is known about factors that alter mutp53 stability and its oncogenic GOF activities. In this review article, we primarily summarize key regulators of mutp53 stability/activities, including genotoxic stress, post-translational modifications, ubiquitin ligases, and molecular chaperones, as well as a single nucleotide polymorphism (SNP) and dimer-forming mutations in mutp53.

Dense Liquid Condensates Host the Nucleation of Tumor Suppressor p53 Fibrils

2018 ◽  
Author(s):  
Mohammad S. Safari ◽  
Zhiqing Wang ◽  
Kunaal Tailor ◽  
Anatoly B. Kolomeisky ◽  
Jacinta C. Conrad ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor P53 ◽  
Dense Liquid

The Sumoylation Modulated Tumor Suppressor p53 Regulates Cell Cycle Checking Genes to Mediate Lens Differentiation

2019 ◽  
Vol 18 (8) ◽  
pp. 556-565 ◽  
Author(s):  
Xiangcheng Tang ◽  
Zhigang Chen ◽  
Mi Deng ◽  
Ling Wang ◽  
Qian Nie ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Tumor Suppressor P53

p22/PACAP Response Gene 1 (PRG1): A Putative Target Gene for the Tumor Suppressor p53

1998 ◽  
Vol 865 (1 VIP, PACAP, A) ◽  
pp. 27-36 ◽  
Author(s):  
HEINER SCHAFER ◽  
ANNA TRAUZOLD ◽  
THORSTEN SEBENS ◽  
WOLFGANG DEPPERT ◽  
ULRICH R. FOLSCH ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Target Gene ◽  
Tumor Suppressor P53 ◽  
Putative Target Gene ◽  
Response Gene ◽  
Putative Target
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