Regulation of p73 by c-Abl through the p38 MAP kinase pathway

Sánchez‐Prieto, Ricardo; Sanchez-Arevalo, Victor Javier; Servitja, Joan‐Marc; Gutkind, J. Silvio

doi:10.1038/sj.onc.1205134

Cited by 104 publications

(71 citation statements)

References 31 publications

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“…c-Abl activated by cisplatin can also upregulates the MEKK-MKK-JNK pathway (Kharbanda et al, 2000), but the implied association between this specific MAPK pathway and p73 has been uncertain previously. However, the case for this association has been strengthened by recent evidence, which shows that activation of p73 by c-Abl also requires the activity of p38 as a representative of the MAPK subfamily member (Sanchez-Prieto et al, 2002).…”

Section: Induction Of Apoptosismentioning

confidence: 95%

Cisplatin: mode of cytotoxic action and molecular basis of resistance

2003

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Cisplatin is one of the most potent antitumor agents known, displaying clinical activity against a wide variety of solid tumors. Its cytotoxic mode of action is mediated by its interaction with DNA to form DNA adducts, primarily intrastrand crosslink adducts, which activate several signal transduction pathways, including those involving ATR, p53, p73, and MAPK, and culminate in the activation of apoptosis. DNA damage-mediated apoptotic signals, however, can be attenuated, and the resistance that ensues is a major limitation of cisplatinbased chemotherapy. The mechanisms responsible for cisplatin resistance are several, and contribute to the multifactorial nature of the problem. Resistance mechanisms that limit the extent of DNA damage include reduced drug uptake, increased drug inactivation, and increased DNA adduct repair. Origins of these pharmacologicbased mechanisms, however, are at the molecular level. Mechanisms that inhibit propagation of the DNA damage signal to the apoptotic machinery include loss of damage recognition, overexpression of HER-2/neu, activation of the PI3-K/Akt (also known as PI3-K/PKB) pathway, loss of p53 function, overexpression of antiapoptotic bcl-2, and interference in caspase activation. The molecular signature defining the resistant phenotype varies between tumors, and the number of resistance mechanisms activated in response to selection pressures dictates the overall extent of cisplatin resistance.

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Section: Induction Of Apoptosismentioning

confidence: 95%

Cisplatin: mode of cytotoxic action and molecular basis of resistance

2003

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“…Gemcitabine has also been shown to activate p38 MAPK (56). c-Abl phosphorylates, stabilizes, and activates p73 and, moreover, the p38 MAPK cascade mediates this response (23,57). Because p73 has also recently been implicated in c-Abl induction of apoptosis following DNA damage (23), it was for 2 h, washed, and incubated in fresh medium for an additional 24 h. Cell lysates were fractionated on SDS-PAGE gels and were analyzed by Western blotting using antibodies against p73, p53, and actin.…”

Section: Discussionmentioning

confidence: 99%

c-Abl-independent p73 stabilization during gemcitabine- or 4′-thio-β-d-arabinofuranosylcytosine–induced apoptosis in wild-type and p53-null colorectal cancer cells

Thottassery

Westbrook

Someya

et al. 2006

Molecular Cancer Therapeutics

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“…In this case, c-Abl kinase may provide an explanation. It has been found that c-Abl can activate p38 through MKK6 [72][73][74] , and JNK by translocating from nucleus to cytoplasm to phosphorylate hematopoietic progenitor kinase (HPK1), an upstream kinase of JNK [75] . Therefore, c-Abl may fulfill a role as the message carrier to transduce signals between subcellular locations.…”

Section: Regulation Of the Tumor Suppressor P53 Proteinmentioning

confidence: 99%

ATM and ATR: Sensing DNA damage

Yang¹,

Xu²,

Huang³

et al. 2004

WJG

118

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Cellular response to genotoxic stress is a very complex process, and it usually starts with the "sensing" or "detection" of the DNA damage, followed by a series of events that include signal transduction and activation of transcription factors. The activated transcription factors induce expressions of many genes which are involved in cellular functions such as DNA repair, cell cycle arrest, and cell death. There have been extensive studies from multiple disciplines exploring the mechanisms of cellular genotoxic responses, which have resulted in the identification of many cellular components involved in this process, including the mitogen-activated protein kinases (MAPKs) cascade. Although the initial activation of protein kinase cascade is not fully understood, human protein kinases ATM (ataxia-telangiectasia, mutated) and ATR (ATM and Rad3-related) are emerging as potential sensors of DNA damage. Current progresses in ATM/ATR research and related signaling pathways are discussed in this review, in an effort to facilitate a better understanding of genotoxic stress response.

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Regulation of p73 by c-Abl through the p38 MAP kinase pathway

Cited by 104 publications

References 31 publications

Cisplatin: mode of cytotoxic action and molecular basis of resistance

Cisplatin: mode of cytotoxic action and molecular basis of resistance

c-Abl-independent p73 stabilization during gemcitabine- or 4′-thio-β-d-arabinofuranosylcytosine–induced apoptosis in wild-type and p53-null colorectal cancer cells

ATM and ATR: Sensing DNA damage

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