c‐Myc‐dependent etoposide‐induced apoptosis involves activation of Bax and caspases, and PKCdelta signaling

Albihn, Ami; Lovén, Jakob; Ohlsson, Johan; Osorio, Lyda M.; Henriksson, Marie Arsenian

doi:10.1002/jcb.20816

Cited by 42 publications

(51 citation statements)

References 55 publications

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“…c-Myc seems essential for the induction of apoptosis by sublethal doses of drug but not required in cases when the apoptotic stimuli is sufficient to trigger apoptosis (Grassilli et al, 2004;Albihn et al, 2006). This is consistent with data demonstrating that low drug doses can have a cytostatic rather than a cytotoxic effect, a condition in which endogenous c-Myc expression is usually down-regulated and, if overexpressed, it can trigger apoptosis.…”

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confidence: 85%

γ-Glutamylcysteine Synthetase Mediates the c-Myc-Dependent Response to Antineoplastic Agents in Melanoma Cells

Benassi¹,

Zupi²,

Biroccio³

2007

Mol Pharmacol

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Section: Downloaded Fromsupporting

confidence: 85%

γ-Glutamylcysteine Synthetase Mediates the c-Myc-Dependent Response to Antineoplastic Agents in Melanoma Cells

Benassi¹,

Zupi²,

Biroccio³

2007

Mol Pharmacol

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“…To determine if lysine-acetylation of the c-MYC oncoprotein is required for its cooperation with p30 II (Awasthi et al, 2005), we performed in vitro cell transformation/foci-formation assays using c-myc −/− HO15.19 rodent fibroblasts which are knocked out for the c-myc gene (Albihn et al, 2006; Mateyak et al, 1997). The cultures were cotransfected with CMV-HTLV-1 p30 II -GFP or a pcDNA3.1-GFP control, and either CβF-wildtype c-MYC or expression constructs for the acetylation-impaired Lys→Arg mutants, c-MYC K323R/K417R (Patel et al, 2004) or c-MYC R5 (Faiola et al, 2005).…”

Section: Resultsmentioning

confidence: 99%

Acetylation of the c-MYC oncoprotein is required for cooperation with the HTLV-1 p30 II accessory protein and the induction of oncogenic cellular transformation by p30 II /c-MYC

Romeo

Kim

et al. 2015

Virology

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The human T-cell leukemia retrovirus type-1 (HTLV-1) p30II protein is a multifunctional latency-maintenance factor that negatively regulates viral gene expression and deregulates host signaling pathways involved in aberrant T-cell growth and proliferation. We have previously demonstrated that p30II interacts with the c-MYC oncoprotein and enhances c-MYC-dependent transcriptional and oncogenic functions. However, the molecular and biochemical events that mediate the cooperation between p30II and c-MYC remain to be completely understood. Herein we demonstrate that p30II induces lysine-acetylation of the c-MYC oncoprotein. Acetylation-defective c-MYC Lys→Arg substitution mutants are impaired for oncogenic transformation with p30II in c-myc−/− HO15.19 fibroblasts. Using dual-chromatin-immunoprecipitations (dual-ChIPs), we further demonstrate that p30II is present in c-MYC-containing nucleoprotein complexes in HTLV-1-transformed HuT-102 T-lymphocytes. Moreover, p30II inhibits apoptosis in proliferating cells expressing c-MYC under conditions of genotoxic stress. These findings suggest that c-MYC-acetylation is required for the cooperation between p30II/c-MYC which could promote proviral replication and contribute to HTLV-1-induced carcinogenesis.

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“…For example, c-myc is an established oncogene in various types of cancer 35,36 however, overexpression of c-myc surprisingly sensitizes cells to apoptosis. [37][38][39] E2F1 is another transcription factor that governs cell cycle progression and also regulates apoptosis under conditions of genotoxic stress. 40 PELP1 overexpressing human breast cancer cells undergo significantly more apoptosis when treated with 9-cis-RA.…”

Section: Resultsmentioning

confidence: 99%

Proline, glutamic acid and leucine-rich protein-1 is essential for optimal p53-mediated DNA damage response

et al. 2014

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, glutamic acid-and leucine-rich protein-1 (PELP1) is a scaffolding oncogenic protein that functions as a coregulator for a number of nuclear receptors. p53 is an important transcription factor and tumor suppressor that has a critical role in DNA damage response (DDR) including cell cycle arrest, repair or apoptosis. In this study, we found an unexpected role for PELP1 in modulating p53-mediated DDR. PELP1 is phosphorylated at Serine1033 by various DDR kinases like ataxia-telangiectasia mutated, ataxia telangiectasia and Rad3-related or DNAPKc and this phosphorylation of PELP1 is important for p53 coactivation functions. PELP1-depleted p53 (wild-type) breast cancer cells were less sensitive to various genotoxic agents including etoposide, camptothecin or c-radiation. PELP1 interacts with p53, functions as p53-coactivator and is required for optimal activation of p53 target genes under genomic stress. Overall, these studies established a new role of PELP1 in DDRs and these findings will have future implications in our understanding of PELP1's role in cancer progression. Cell Death and Differentiation (2014) 21, 1409-1418; doi:10.1038/cdd.2014.55; published online 2 May 2014 p53 is considered as the guardian of genomic integrity and has an important role in initiating cellular response to various genomic stresses such as cell cycle arrest, senescence, DNA repair and apoptosis.1,2 Loss of p53 or mutations in p53 is observed in 450% of the cases of all cancers.3-5 Stabilization of p53 upon genomic stress and activation of its transcription functions are vital for its central role in the DNA damage/ genomic stress response and in its tumor-suppressive functions.6,7 Upon genomic stress, p53 is stabilized and activated because of a decreased interaction with its E3-ligase MDM2.8 Activated p53 then upregulates expression of target genes, such as p21/WAF1, GADD45, PUMA and NOXA, all of which are important in the cellular decisions for cell cycle arrest or apoptosis. Post-translational modifications of p53, including phosphorylation, acetylation, ubiquitinylation and methylation, 10-12 and interactions with several cofactors 13,14 have a critical role in the p53-mediated transcriptional response to the DNA damage response (DDR). Proline-, glutamic acid-and leucine-rich protein-1 (PELP1), a large multi-domain protein, modulates a number of biological processes and several pathways including estrogen signaling, and cancer progression. 17 It promotes cell proliferation by enhancing G1 to S phase progression via its interactions with the pRb/E2F pathway.25 PELP1 localizes to the nucleolus and has an important role in ribosomal biogenesis.26 PELP1 signaling is also implicated in apoptosis and differentiation, and PELP1 functions as a coactivator of RXR homodimers and RXR-PPAR heterodimers.27 Although PELP1's role in both cell proliferation and differentiation is evident, it is not known how PELP1 would affect p53-mediated DDR functions and whether PELP1 status would affect sensitivity to various genomic stresses.In this study,...

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c‐Myc‐dependent etoposide‐induced apoptosis involves activation of Bax and caspases, and PKCdelta signaling

Cited by 42 publications

References 55 publications

γ-Glutamylcysteine Synthetase Mediates the c-Myc-Dependent Response to Antineoplastic Agents in Melanoma Cells

γ-Glutamylcysteine Synthetase Mediates the c-Myc-Dependent Response to Antineoplastic Agents in Melanoma Cells

Acetylation of the c-MYC oncoprotein is required for cooperation with the HTLV-1 p30 II accessory protein and the induction of oncogenic cellular transformation by p30 II /c-MYC

Proline, glutamic acid and leucine-rich protein-1 is essential for optimal p53-mediated DNA damage response

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