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ARF antagonizes the ability of Miz-1 to inhibit p53-mediated transactivation

Miao, L. and Song, Z. and Jin, L. and Zhu, Y. M. and Wen, L. P. and Wu, M. (2010) ARF antagonizes the ability of Miz-1 to inhibit p53-mediated transactivation. Oncogene, 29 (5). pp. 711-722. ISSN 0950-9232.

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Although Myc-interacting zinc-finger protein-1 (Miz-1) is known to be a poxvirus and zinc-finger (POZ) transcription factor required for Myc transcriptional repression, additional regulatory function of Miz-1 is less well understood. Using a yeast two-hybrid screen, we identified human alternate reading frame (ARF) protein as a novel interaction partner of Miz-1. The zinc-finger domain of Miz-1 is involved in its binding to ARF. In addition, we found that Miz-1 was able to interact with p53 through its DNA-binding domain, thus to diminish the binding of p53 to its target promoter and inhibit p53-mediated gene transcription. Interestingly, the Miz-1-regulated p53 transcriptional suppression does not require the presence of ARF or Mdm2. Importantly, ARF and p53 were found to competitively bind to Miz-1 in regulating p53-mediated transcription, and this conclusion was verified by both in vitro binding assay and competitive chromatin immunoprecipitation assay using a bona fide p53 endogenous Bax and Puma promoters. Thus, our study reveals that Miz-1 acts as a p53 suppressor by interfering with p53 DNA-binding ability, and ARF is able to counteract the suppression of Miz-1 on p53 by direct binding to Miz-1, suggesting that Miz-1 is a novel mediator in the ARF-p53 pathway.

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Additional Information:© 2010 Macmillan Publishers Limited. Received 6 April 2009; Revised 24 August 2009; Accepted 30 August 2009; Published online 9 November 2009. We thank Dr Nickie Chan for English checking and Dr Ratna B Ray for the plasmid pGL3-13-p53-Luc. This study was supported by grants from the National Natural Science Foundation of China (30530200, 30728003 and 30871290), the Ministry of Science and Technology of China (2006CB933300, 2006CB0N1402, and 2006CB910300) and the Chinese Academy of Sciences (KSCX1-YW-R-57).
Funding AgencyGrant Number
National Natural Science Foundation of China30530200
National Natural Science Foundation of China30728003
National Natural Science Foundation of China30871290
Ministry of Science and Technology of China2006CB933300
Ministry of Science and Technology of China2006CB0N1402
Ministry of Science and Technology of China2006CB910300
Chinese Academy of SciencesKSCX1-YW-R-57
Subject Keywords:p53; Miz-1; p14ARF; protein/protein interaction; transcription
Issue or Number:5
Record Number:CaltechAUTHORS:20100301-102009616
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:17615
Deposited By: Tony Diaz
Deposited On:10 Mar 2010 18:09
Last Modified:03 Oct 2019 01:30

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