Article: XIAP-associated factor 1 (XAF1), a novel target of p53, enhances p53-mediated apoptosis via post-translational modification
| Title | XIAP-associated factor 1 (XAF1), a novel target of p53, enhances p53-mediated apoptosis via post-translational modification | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Zou, B1 2 Chim, CS1 Pang, R1 Zeng, H2 Dai, Y1 Zhang, R1 Lam, CSC1 Tan, VPY1 Hung, IFN1 Lan, HY3 Wong, BCY1 | ||||||
| Keywords | Apoptosis Colon cancer Gastric cancer P53 XAF1 | ||||||
| Issue Date | 2012 | ||||||
| Publisher | John Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0899-1987/ | ||||||
| Citation | Molecular Carcinogenesis, 2012, v. 51 n. 5, p. 422-432 [How to Cite?] DOI: http://dx.doi.org/10.1002/mc.20807 | ||||||
| Abstract | The 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. | ||||||
| ISSN | 0899-1987 2011 Impact Factor: 3.164 2011 SCImago Journal Rankings: 0.347 | ||||||
| DOI | http://dx.doi.org/10.1002/mc.20807 | ||||||
| ISI Accession Number ID | WOS:000302623000006
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). | ||||||
| References | References in Scopus |
| dc.contributor.author | Zou, B | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Chim, CS | ||||||
| dc.contributor.author | Pang, R | ||||||
| dc.contributor.author | Zeng, H | ||||||
| dc.contributor.author | Dai, Y | ||||||
| dc.contributor.author | Zhang, R | ||||||
| dc.contributor.author | Lam, CSC | ||||||
| dc.contributor.author | Tan, VPY | ||||||
| dc.contributor.author | Hung, IFN | ||||||
| dc.contributor.author | Lan, HY | ||||||
| dc.contributor.author | Wong, BCY | ||||||
| dc.date.accessioned | 2011-08-26T14:23:59Z | ||||||
| dc.date.available | 2011-08-26T14:23:59Z | ||||||
| dc.date.issued | 2012 | ||||||
| dc.description.abstract | The 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.nature | Link_to_subscribed_fulltext | ||||||
| dc.identifier.citation | Molecular Carcinogenesis, 2012, v. 51 n. 5, p. 422-432 [How to Cite?] DOI: http://dx.doi.org/10.1002/mc.20807 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1002/mc.20807 | ||||||
| dc.identifier.epage | 432 | ||||||
| dc.identifier.hkuros | 189629 | ||||||
| dc.identifier.hkuros | 173757 | ||||||
| dc.identifier.isi | WOS:000302623000006
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.issn | 0899-1987 2011 Impact Factor: 3.164 2011 SCImago Journal Rankings: 0.347 | ||||||
| dc.identifier.issue | 5 | ||||||
| dc.identifier.pmid | 21678496 | ||||||
| dc.identifier.scopus | eid_2-s2.0-84859776957 | ||||||
| dc.identifier.spage | 422 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/137367 | ||||||
| dc.identifier.volume | 51 | ||||||
| dc.language | eng | ||||||
| dc.publisher | John Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0899-1987/ | ||||||
| dc.publisher.place | United States | ||||||
| dc.relation.ispartof | Molecular Carcinogenesis | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.subject.mesh | Apoptosis - genetics | ||||||
| dc.subject.mesh | Cell Line, Tumor | ||||||
| dc.subject.mesh | Colonic Neoplasms - genetics - metabolism | ||||||
| dc.subject.mesh | Gene Expression Regulation, Neoplastic | ||||||
| dc.subject.mesh | Humans | ||||||
| dc.subject.mesh | Intracellular Signaling Peptides and Proteins - genetics - metabolism | ||||||
| dc.subject.mesh | Neoplasm Proteins - genetics - metabolism | ||||||
| dc.subject.mesh | Promoter Regions, Genetic | ||||||
| dc.subject.mesh | Protein Processing, Post-Translational - genetics | ||||||
| dc.subject.mesh | Stomach Neoplasms - genetics - metabolism | ||||||
| dc.subject.mesh | Tumor Suppressor Protein p53 - genetics - metabolism | ||||||
| dc.subject | Apoptosis | ||||||
| dc.subject | Colon cancer | ||||||
| dc.subject | Gastric cancer | ||||||
| dc.subject | P53 | ||||||
| dc.subject | XAF1 | ||||||
| dc.title | XIAP-associated factor 1 (XAF1), a novel target of p53, enhances p53-mediated apoptosis via post-translational modification | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong
- Guangzhou Medical College
- Chinese University of Hong Kong

