Article: XIAP-associated factor 1 (XAF1), a novel target of p53, enhances p53-mediated apoptosis via post-translational modification

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TitleXIAP-associated factor 1 (XAF1), a novel target of p53, enhances p53-mediated apoptosis via post-translational modification
AuthorsZou, B1 2
Chim, CS1
Pang, R1
Zeng, H2
Dai, Y1
Zhang, R1
Lam, CSC1
Tan, VPY1
Hung, IFN1
Lan, HY3
Wong, BCY1
KeywordsApoptosis
Colon cancer
Gastric cancer
P53
XAF1
Issue Date2012
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0899-1987/
CitationMolecular Carcinogenesis, 2012, v. 51 n. 5, p. 422-432 [How to Cite?]
DOI: http://dx.doi.org/10.1002/mc.20807
AbstractThe role of X chromosome-linked inhibitor of apoptosis protein (XIAP)-associated factor 1 (XAF1) in mediating apoptosis has been reported but the underlying mechanism remains unclear. The present study was designed to examine the putative interaction between XAF1 and p53 and the functional importance of this interaction in regulation of apoptosis in human gastric and colon cancer cells. We first identified XAF1 as a novel target gene of p53 by the chromatin immunoprecipitation (CHIP) assay and demonstrated that wild-type p53, but not mutant p53, down-regulated XAF1 at both mRNA and protein levels, which acted mostly under the condition of high expression of XAF1 and was associated with the physical interaction between p53 and the XAF1 promoter. We also found that the over-expression of XAF1 led to activation of wild-type p53 via post-translational modification in cells with or without DNA damage, which resulting in p53 nuclear accumulation and its increased transcriptional activity and enhancing p53-dependent apoptosis. These findings suggest that a potential novel feedback loop exists between XAF1 and wild-type p53. © 2011 Wiley Periodicals, Inc.
ISSN0899-1987
2011 Impact Factor: 3.164
2011 SCImago Journal Rankings: 0.347
DOIhttp://dx.doi.org/10.1002/mc.20807
ISI Accession Number IDWOS:000302623000006
Funding AgencyGrant Number
University of Hong KongHKU-200807176136
Science and Technology Programme of Guangzhou, China2008J1-C261-3
Funding Information:

This study was supported by the grants of Small Project Funding (HKU-200807176136), Simon K.Y. Lee Endowed Professorship Research Fund, and the Outstanding Researcher Award Fund of the University of Hong Kong, and the Science and Technology Programme of Guangzhou, China (2008J1-C261-3).

ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorZou, B
dc.contributor.authorChim, CS
dc.contributor.authorPang, R
dc.contributor.authorZeng, H
dc.contributor.authorDai, Y
dc.contributor.authorZhang, R
dc.contributor.authorLam, CSC
dc.contributor.authorTan, VPY
dc.contributor.authorHung, IFN
dc.contributor.authorLan, HY
dc.contributor.authorWong, BCY
dc.date.accessioned2011-08-26T14:23:59Z
dc.date.available2011-08-26T14:23:59Z
dc.date.issued2012
dc.description.abstractThe role of X chromosome-linked inhibitor of apoptosis protein (XIAP)-associated factor 1 (XAF1) in mediating apoptosis has been reported but the underlying mechanism remains unclear. The present study was designed to examine the putative interaction between XAF1 and p53 and the functional importance of this interaction in regulation of apoptosis in human gastric and colon cancer cells. We first identified XAF1 as a novel target gene of p53 by the chromatin immunoprecipitation (CHIP) assay and demonstrated that wild-type p53, but not mutant p53, down-regulated XAF1 at both mRNA and protein levels, which acted mostly under the condition of high expression of XAF1 and was associated with the physical interaction between p53 and the XAF1 promoter. We also found that the over-expression of XAF1 led to activation of wild-type p53 via post-translational modification in cells with or without DNA damage, which resulting in p53 nuclear accumulation and its increased transcriptional activity and enhancing p53-dependent apoptosis. These findings suggest that a potential novel feedback loop exists between XAF1 and wild-type p53. © 2011 Wiley Periodicals, Inc.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationMolecular Carcinogenesis, 2012, v. 51 n. 5, p. 422-432 [How to Cite?]
DOI: http://dx.doi.org/10.1002/mc.20807
dc.identifier.doihttp://dx.doi.org/10.1002/mc.20807
dc.identifier.epage432
dc.identifier.hkuros189629
dc.identifier.hkuros173757
dc.identifier.isiWOS:000302623000006
Funding AgencyGrant Number
University of Hong KongHKU-200807176136
Science and Technology Programme of Guangzhou, China2008J1-C261-3
Funding Information:

This study was supported by the grants of Small Project Funding (HKU-200807176136), Simon K.Y. Lee Endowed Professorship Research Fund, and the Outstanding Researcher Award Fund of the University of Hong Kong, and the Science and Technology Programme of Guangzhou, China (2008J1-C261-3).

dc.identifier.issn0899-1987
2011 Impact Factor: 3.164
2011 SCImago Journal Rankings: 0.347
dc.identifier.issue5
dc.identifier.pmid21678496
dc.identifier.scopuseid_2-s2.0-84859776957
dc.identifier.spage422
dc.identifier.urihttp://hdl.handle.net/10722/137367
dc.identifier.volume51
dc.languageeng
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0899-1987/
dc.publisher.placeUnited States
dc.relation.ispartofMolecular Carcinogenesis
dc.relation.referencesReferences in Scopus
dc.subject.meshApoptosis - genetics
dc.subject.meshCell Line, Tumor
dc.subject.meshColonic Neoplasms - genetics - metabolism
dc.subject.meshGene Expression Regulation, Neoplastic
dc.subject.meshHumans
dc.subject.meshIntracellular Signaling Peptides and Proteins - genetics - metabolism
dc.subject.meshNeoplasm Proteins - genetics - metabolism
dc.subject.meshPromoter Regions, Genetic
dc.subject.meshProtein Processing, Post-Translational - genetics
dc.subject.meshStomach Neoplasms - genetics - metabolism
dc.subject.meshTumor Suppressor Protein p53 - genetics - metabolism
dc.subjectApoptosis
dc.subjectColon cancer
dc.subjectGastric cancer
dc.subjectP53
dc.subjectXAF1
dc.titleXIAP-associated factor 1 (XAF1), a novel target of p53, enhances p53-mediated apoptosis via post-translational modification
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong
  2. Guangzhou Medical College
  3. Chinese University of Hong Kong