The RAX/PACT-PKR stress response pathway promotes p53 sumoylation and activation, leading to G<sub>1</sub>arrest

Bennett, Richard L.; Pan, Yu; Christian, Jamie; Teng, Hui; May, W. Stratford

doi:10.4161/cc.11.2.18999

Cited by 42 publications

(41 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, sentrin-specific proteinase 1 (SENP1) inhibited SIRT1 activity by interacting and desumoylating SIRT1, thereby promoting stress-induced apoptosis (26). Of these, CK2 and SENP1 have been shown to regulate p53 activity either directly or indirectly (27,28). Our results show that the inactivation of DBC1 or SIRT1 reduced HCC cell viability and that DBC1 does not negatively regulate SIRT1 activity in HCC cells (Figs.…”

Section: Discussionsupporting

confidence: 48%

DBC1 does not function as a negative regulator of SIRT1 in liver cancer

et al. 2012

View full text Add to dashboard Cite

Abstract. The putative tumor suppressor, DBC1 (deleted in breast cancer-1), was recently found to negatively regulate SIRT1 in vitro and in vivo, but the mechanism whereby DBC1 regulates SIRT1 in liver cancer remains to be elucidated. In this study, it was found that although the expression of DBC1 and SIRT1 was not aberrantly regulated in a large cohort of human hepatocellular carcinoma (HCC) patients, these proteins were highly overexpressed in a subset of HCC tissues compared with surrounding non-cancer tissues. In liver cancer, DBC1 and SIRT1 were found to be positively correlated. Inactivation of DBC1 or SIRT1 reduced SNU-182 (a liver cancer cell line) proliferation as determined by MTT viability assays. Notably, although DBC1 functions as a negative regulator of SIRT1 in A549 lung cancer cells since it suppresses the deacetylase activity of the p53 protein, it did not affect the p53 deacetylase activity of SIRT1 in SNU-182 cells. Taken together, we conclude that DBC1 is associated with SIRT1 in HCC, but that it does not inhibit SIRT1.

show abstract

Section: Discussionsupporting

confidence: 48%

DBC1 does not function as a negative regulator of SIRT1 in liver cancer

et al. 2012

View full text Add to dashboard Cite

show abstract

“…As reported for the RAX/PACT-PKR stress-signaling pathway, sumoylation events may be required for p53 phosphorylation. 40 Bennett et al reported that the RAX/PACT protein induces p53 lysine 386 sumoylation through an interaction with SUMO E2 ligase Ubc9 before triggering p53 serine 392 phosphorylation. These two post-translational modifications seemed sufficient to stabilize the transcription factor, enhance its transcriptional activity and trigger G 1 arrest.…”

Section: Methodsmentioning

confidence: 99%

HIPK1 drives p53 activation to limit colorectal cancer cell growth

et al. 2013

View full text Add to dashboard Cite

“…[6][7][8] We and others have reported that activated PKR can regulate proliferation and apoptosis by phosphorylation of eukaryotic initiation factor 2a (eIF2a) to inhibit new protein synthesis, activation of a PP2A-dependent Bcl2 dephosphorylation mechanism resulting in mitochondrial dysfunction, and activation of signaling pathways such as nuclear factor kB, p53, and signal transducer and activator of transcription 1. 6,[9][10][11][12] Significantly, loss of the PKR expression/ activity has been associated with increased growth of human breast carcinoma, nonsmall cell lung cancer, B-cell chronic lymphocytic leukemia, and T-cell acute lymphoblastic leukemia, suggesting that the loss of PKR activity may contribute to increased growth and malignancy. [13][14][15][16] In contrast, increased PKR activity may inhibit cell growth and enhance stress responses, leading to apoptosis.…”

Section: Introductionmentioning

confidence: 99%