TAILIEUCHUNG - Retrovirology Research BioMed Central Open Access Induction of p21CIP1/WAF1 expression by human

Retrovirology Research BioMed Central Open Access Induction of p21CIP1/WAF1 expression by human T-lymphotropic virus type 1 Tax requires transcriptional activation and mRNA stabilization Ling Zhang, Huijun Zhi, Meihong Liu, Yu-Liang Kuo and Chou-Zen Giam* Address: Department of Microbiology and Immunology, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD 20814, USA Email: Ling Zhang - zhangling@; Huijun Zhi - hzhi@; Meihong Liu - lmeihong@; YuLiang Kuo - ylkuo622@; Chou-Zen Giam* - cgiam@ * Corresponding author Published: 8 April 2009 Retrovirology 2009, 6:35 doi: Received: 17 November 2008 Accepted: 8 April 2009 This article is available from: © 2009 Zhang et al; licensee BioMed Central Ltd. This is an. | Retrovirology BioMed Central Research Induction of p21CIP1 WAF1 expression by human T-lymphotropic virus type 1 Tax requires transcriptional activation and mRNA stabilization Ling Zhang Huijun Zhi Meihong Liu Yu-Liang Kuo and Chou-Zen Giam Open Access Address Department of Microbiology and Immunology Uniformed Services University 4301 Jones Bridge Road Bethesda MD 20814 USA Email Ling Zhang - zhangling@ Huijun Zhi - hzhi@ Meihong Liu - lmeihong@ Yu- Liang Kuo - ylkuo622@ Chou-Zen Giam - cgiam@ Corresponding author Published 8 April 2009 Received 17 November 2008 Retrovirology 2009 6 35 doi 1742-4690-6-35 Accepted 8 April 2009 This article is available from http content 6 1 35 2009 Zhang et al licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License http licenses by which permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited. Abstract HTLV-1 Tax can induce senescence by up-regulating the levels of cyclin-dependent kinase inhibitors p21CIP1 WAF1 and p27KIP1. Tax increases p27KIP1 protein stability by activating the anaphase promoting complex cyclosome APC C precociously causing degradation of Skp2 and inactivation of SCFSkp2 the E3 ligase that targets p27KIP1. The rate of p21CIP1 WAF1 protein turnover however is unaffected by Tax. Rather the mRNA of p21CIP1 WAF1 is greatly up-regulated. Here we show that Tax increases p21 mRNA expression by transcriptional activation and mRNA stabilization. Transcriptional activation of p21CIP1 WAF1 by Tax occurs in a p53-independent manner and requires two tumor growth factor-P-inducible Sp1 binding sites in the -84 to -60 region of the p21CIP1 WAF1 promoter. Tax binds Sp1 directly and the CBP p300-binding activity of Tax is required for p21CIP1 WAF1 trans-activation. Tax also increases .

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