Inhibition of HTLV-1 Transcription by Cyclin Dependent Kinase Inhibitors

Overview

Journal Mol Cell Biochem

Publisher Springer

Specialty Biochemistry

Date 2002 Sep 19

PMID 12236581

Citations 12

Authors

Lai Wang

Longwen Deng

Kaili Wu

Cynthia de la Fuente

Dai Wang

Kylene Kehn

Anil Maddukuri

Shanese Baylor

Francisco Santiago

Emmanuel Agbottah

Sylviane Trigon

Michel Morange

Renaud Mahieux

Fatah Kashanchi

Affiliations

Soon will be listed here.

Abstract

HTLV-1 is the etiologic agent for adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), where viral replication and transformation are largely dependent upon modification of regulatory and host cell cycle proteins. The mechanism of HTLV-1 transformation appears to be distinct from that of many known chronic or acute leukemia viruses and is related to the viral activator Tax. Here we show that cyclin E, can associate tightly with the coactivator p300 and Pol II complex in HTLV-1 infected cells. The cyclin E associated complex is kinase active and phosphorylates the carboxy terminal domain of RNA Pol II. More importantly, p21/Waf1, a well-known cdk inhibitor at the G1/S border, inhibits transcription of HTLV-1 in both transfections and in in vitro transcription assays. Finally, specific cdk chemical inhibitors, functionally similar to cellular cdkIs, such as p21/Waf1 which inhibits cyclin E/cdk2 activity, also inhibit transcription of the HTLV-1 promoter. In particular, Purvalanol A, with an IC50 of 0.035 microm inhibits activated, but not basal transcription, as well as HTLV-1 infected cells. Collectively, the role of cyclin E/cdk2 in HTLV-1 infected cells and its involvement in RNA Pol II phosphorylation is discussed.

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