Calcium-dependent enhancement of transcription of p300 by human T-lymphotropic type 1 p12^I

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• 作者：Amrithraj M. Nair ; Bindhu Michael ; Antara Datta ; Soledad Fernandez and Michael D. Lairmore
• 关键词：Calcium ; p300 ; Retrovirus ; HTLV-1 ; Accessory protein ; Transcription
• 刊名：Virology
• 出版年：2006
• 期刊代码：108_00426822
• 类别：imm
• 出版时间：30 September 2006
• 卷：353
• 期：2
• 页码：247-257
• 文件大小：452 K

摘要

Human T-lymphotropic virus type 1 (HTLV-1) p12^I localizes to the endoplasmic reticulum and Golgi causing sustained release of calcium, T cell activation, and enhanced expression of several calcium-regulated genes. In recent microarray studies, p300 mRNA was increased in T cells expressing p12^I. The co-activator p300 is a key regulator of cellular and viral transcription; however, factors that influence its transcriptional regulation are less well studied. We hypothesized that the transcription of p300 is calcium dependent and that sustained low magnitude increases in intracellular calcium may enhance the transcription of p300. Herein, we report enhanced expression of p300 in T cells by p12^I in a calcium-dependent, but calcineurin-independent manner. Sustained low magnitude calcium release induced by ionomycin in T cells was sufficient to increased mRNA and protein levels of p300 resulting in enhanced transcription from a p300-dependent promoter. Promoter analysis of the p300 gene was used to predict calcium-responsive transcription factor binding sites. Using mutant forms of p12^I, we demonstrate that ER localization of the viral protein is required to increase p300. In addition, p12^I reversed the repression of HTLV-1 LTR-driven transcription by HTLV-1 p30^II, a p300-binding protein. HTLV-1 p12^I-mediated enhancement of p300 expression represents a novel mechanism of regulation of cellular gene expression by viral proteins. By targeting a ubiquitous second messenger such as calcium, HTLV-1 p12^I may regulate the expression of the cellular transcriptional co-activator p300 to modulate viral gene expression and promote lymphocyte survival.