Acetylation Is Indispensable for p53 Activation

Tang, Yi; Zhao, Wenhui; Chen, Yue; Zhao, Yingming; Gu, Wei

doi:10.1016/j.cell.2008.06.005

Cited by 242 publications

(377 citation statements)

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“…It has been reported that p53 is regulated by posttranslational modifications including ubiquitination, phosphorylation and methylation and that posttranslational modifications of p53 are associated with its functions, including DNA repair, cell cycle arrest and apoptosis [25]. p53 is ubiquitinated by Mdm2 E3 ligase and acetylation of p53 destabilizes the p53-Mdm2 interaction, suggesting that acetylation of p53 is indispensable for p53 activation [26].…”

Section: Discussionmentioning

confidence: 99%

RNF43 interacts with NEDL1 and regulates p53-mediated transcription

Shinada

Tsukiyama

Sho

et al. 2011

Biochemical and Biophysical Research Communications

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The ubiquitin-proteasomal system plays a crucial role in oncogenesis in colorectal tissues. Recent studies have shown that stability of -catenin, which functions as an oncogene for colorectal cancer, is regulated by ubiquitin-mediated degradation. It has been reported that a putative E3 ubiquitin ligase, RNF43, is highly expressed in human colorectal carcinoma and that RNF43 promotes cell growth. However, the involvement of RNF43 in carcinogenesis has not been fully elucidated. In this study, we found by using yeast two-hybrid screening that RNF43 binds to NEDD-4-like ubiquitin-protein ligase-1 (NEDL1), which enhances pro-apoptotic activity by p53. In addition, we found that RNF43 also interacts with p53 and that RNF43 suppresses transcriptional activity of p53 in H1299 cells and attenuates apoptosis induced by ultraviolet irradiation. These findings suggest that RNF43 is associated with p53-mediated apoptosis in collaboration with NEDL1 in colorectal carcinogenesis.3

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Section: Discussionmentioning

confidence: 99%

RNF43 interacts with NEDL1 and regulates p53-mediated transcription

Shinada

Tsukiyama

Sho

et al. 2011

Biochemical and Biophysical Research Communications

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“…36,37 Interestingly, it has been shown that while p53 acetylation is required for its transactivation activity on several p53 target genes, the Mdm2 promoter is regulated by p53 even in the absence of this post-translational regulation, suggesting that Mdm2 transcription by p53 may involve specific pathways. 38 We identified Ser 392 phosphorylation as a mechanism to specifically tune the expression of genes like Mdm2 and regulate cell survival. In contrast, Met does not modulate the phosphorylation of other Ser residues regulating p53 levels, which would be incompatible with tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Abl interconnects oncogenic Met and p53 core pathways in cancer cells

et al. 2011

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The simplicity of BCR-ABL 'oncogene addiction' characterizing leukemia contrasts with the complexity of solid tumors where multiple 'core pathways', including receptor tyrosine kinases (RTKs) and p53, are often altered. This discrepancy illustrates the limited success of RTK antagonists in solid tumor treatment compared with the impact of Imatinib in BCR-ABL-dependent leukemia. Here, we identified c-Abl as a signaling node interconnecting Met-RTK and p53 core pathways, and showed that its inhibition impairs Met-dependent tumorigenesis. Met ensures cell survival through a new path in which c-Abl and p38-MAPK are employed to elicit p53 phosphorylation on Ser(392) and Mdm2 upregulation. We found a clinical correlation between activated Met, phospho-p53, and Mdm2 levels in human tumors, supporting the role of this path in tumorigenesis. Our findings introduce the concept that RTK-driven tumors may be therapeutically treated by hitting signaling nodes interconnecting core pathways. Moreover, they underline the importance of evaluating the relevance of c-Abl antagonists for combined therapies, based on the tumor signaling signature.Cell Death and Differentiation advance online publication, 1 April 2011; doi:10.1038/cdd.2011.23

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“…The 18 human HDACs may be classified as either zinc-or NAD 1 -dependent and further subclassified into class I (HDAC1, 2, 3, and 8), class II (HDAC4, 5, 6, 7, 9, and 10), class III (including NAD 1 -dependent sirtuins), and class IV (HDAC11) HDACs. As HDACs regulate a wide variety of processes involved in carcinogenesis, multiple mechanisms may explain the clinical activity of HDAC inhibitors [249,250], including altered gene expression of cell-cycle and apoptotic regulatory proteins [251][252][253][254][255], acetylation of nonhistone proteins regulating cell growth and survival [256][257][258][259], angiogenesis [260,261], aggresome formation [262], and DNA repair [263]. In addition, HDAC inhibitors may have important effects on the tumor microenvironment via reactive oxygen species [264,265], enhanced antigen presentation [266] and downregulation of immunomodulatory cytokines, like IL-10 [267].…”

Section: Hdac Inhibitorsmentioning

confidence: 99%

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

Wilcox

2011

American J Hematol

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Disease overview: Cutaneous T‐cell lymphomas are a heterogenous group of T‐cell lymphoproliferative disorders involving the skin, the majority of which may be classified as Mycosis fungoides (MF) or Sézary syndrome (SS).Diagnosis: The diagnosis of MF or SS requires the integration of clinical and histopathologic data.Risk‐adapted therapy: Tumor, node, metastasis, and blood (TNMB) staging remains the most important prognostic factor in MF/SS and forms the basis for a “risk‐adapted,” multidisciplinary approach to treatment. For patients with disease limited to the skin, expectant management or skin‐directed therapies is preferred, as both disease‐specific and overall survival for these patients is favorable. In contrast, patients with advanced‐stage disease with significant nodal, visceral, or blood involvement are generally approached with biologic‐response modifiers, denileukin diftitox, and histone deacetylase inhibitors before escalating therapy to include systemic, single‐agent chemotherapy. Multiagent chemotherapy may be used for those patients with extensive visceral involvement requiring rapid disease control. In highly‐selected patients with disease refractory to standard treatments, allogeneic stem‐cell transplantation may be considered. Am. J. Hematol., 2011. © 2011 Wiley‐Liss, Inc.

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Acetylation Is Indispensable for p53 Activation

Cited by 242 publications

References 0 publications

RNF43 interacts with NEDL1 and regulates p53-mediated transcription

RNF43 interacts with NEDL1 and regulates p53-mediated transcription

Abl interconnects oncogenic Met and p53 core pathways in cancer cells

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

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