tailieunhanh - Báo cáo y học: "The HTLV-1 Tax protein binding domain of cyclin-dependent kinase 4 (CDK4) includes the regulatory PSTAIRE helix"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: "The HTLV-1 Tax protein binding domain of cyclin-dependent kinase 4 (CDK4) includes the regulatory PSTAIRE helix | Retrovirology BioMed Central Research Open Access The HTLV-I Tax protein binding domain of cyclin-dependent kinase 4 CDK4 includes the regulatory PSTAIRE helix Kirsten Fraedrich Birthe Muller and Ralph Grassmann Address Institut fur Klinische und Molekulare Virologie Universitat Erlangen-Nurnberg Schlossgarten 4 D-91054 Erlangen Germany Email Kirsten Fraedrich - Birthe Muller - MuellerBi@ Ralph Grassmann - rfgrassm@ Corresponding author Published 15 September 2005 Received 12 July 2005 Accepted 15 September 2005 Retrovirology 2005 2 54 doi 186 1742-4690-2-54 This article is available from http content 2 1 54 2005 Fraedrich 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 Background The Tax oncoprotein of human T-cell leukemia virus type 1 HTLV-1 is leukemogenic in transgenic mice and induces permanent T-cell growth in vitro. It is found in active CDK holoenzyme complexes from adult T-cell leukemia-derived cultures and stimulates the G1-to-S phase transition by activating the cyclin-dependent kinase CDK CDK4. The Tax protein directly and specifically interacts with CDK4 and cyclin D2 and binding is required for enhanced CDK4 kinase activity. The protein-protein contact between Tax and the components of the cyclin D CDK complexes increases the association of CDK4 and its positive regulatory subunit cyclin D and renders the complex resistant to p21CIP inhibition. Tax mutants affecting the N-terminus cannot bind cyclin D and CDK4. Results To analyze whether the N-terminus of Tax is capable of CDK4-binding in vitro binding - pull down - and mammalian two-hybrid analyses were performed. These experiments revealed that