HTLV-I p30 inhibits multiple S phase entry checkpoints, decreases cyclin E-CDK2 interactions and delays cell cycle progression

• Published in: Molecular cancer Vol. 9; no. 1; p. 302
• Main Authors: Baydoun, Hicham H, Pancewicz, Joanna, Bai, Xuetao, Nicot, Christophe
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 23.11.2010; BioMed Central; BMC
• Subjects: Blotting, Western; Cell cycle; Cell Cycle - genetics; Cell Cycle - physiology; Cell Line; Cloning; Cyclin E - genetics; Cyclin E - metabolism; Cyclin-Dependent Kinase 2 - genetics; Cyclin-Dependent Kinase 2 - metabolism; Experiments; Flow Cytometry; Gene expression; Genetic aspects; Health aspects; HeLa Cells; HTLV-I (Virus); Human T-lymphotropic virus 1; Human T-lymphotropic virus 1 - genetics; Human T-lymphotropic virus 1 - metabolism; Human T-lymphotropic virus 2; Humans; Immunoprecipitation; Kinases; Leukemia; Phase transitions; Protein Binding; Proteins; Retroviridae Proteins - genetics; Retroviridae Proteins - metabolism; Reverse Transcriptase Polymerase Chain Reaction; S Phase - genetics; S Phase - physiology; Studies; United States
• ISSN: 1476-4598; 1476-4598
• DOI: 10.1186/1476-4598-9-302

Human T-cell leukemia virus type I (HTLV-I) has efficiently adapted to its host and establishes a persistent infection characterized by low levels of viral gene expression and slow proliferation of HTLV-I infected cells over decades. We have previously found that HTLV-I p30 is a negative regulator of virus expression. In this study we show that p30 targets multiple cell cycle checkpoints resulting in a delayed entry into S phase. We found that p30 binds to cyclin E and CDK2 and prevents the formation of active cyclin E-CDK2 complexes. In turn, this decreases the phosphorylation levels of Rb and prevents the release of E2F and its transcriptional activation of genes required for G1/S transition. Our studies also show that HTLV-II p28 does not bind cyclin E and does not affect cell cycle progression. In contrast to HTLV-I, the HTLV-II-related retrovirus is not oncogenic in humans. Here we report that the HTLV-I p30 delays cell cycle progression while its homologue, HTLV-II p28, does not, providing evidence for important differences between these two related retrovirus proteins.