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HTLV‐1 Tax protein interacts with cyclin‐dependent kinase inhibitor p16INK4A and counteracts its inhibitory activity towards CDK4.
Author(s) -
Suzuki T.,
Kitao S.,
Matsushime H.,
Yoshida M.
Publication year - 1996
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1996.tb00505.x
Subject(s) - biology , inhibitory postsynaptic potential , cyclin dependent kinase 4 , cyclin dependent kinase 2 , microbiology and biotechnology , cyclin dependent kinase , cancer research , protein kinase a , kinase , genetics , cell cycle , gene , neuroscience
Tax, a regulatory protein of human T‐cell leukemia virus type 1 (HTLV‐1), is an oncoprotein which immortalizes human T cells and induces tumors in transgenic mice. These effects may be due to its interaction with cellular proteins, consisting of several transcription factors including CREB, NF‐kappa B and SRF, and the transcriptional inhibitor, I kappa B. Here, we found that Tax binds to a cyclin‐dependent kinase inhibitor, p16INK4A, which has ankyrin motifs similar to I kappa B. p16INK4A binds to the cyclin‐dependent kinases, CDK4 and CDK6, and inhibits their activity, resulting in suppression of G1 phase progression. The binding of Tax to p16INK4a induced a reduction in the p16INK4A‐CDK4 complex, with subsequent activation of CDK4 kinase. Tax also suppressed p16INK4A‐mediated inhibition of U2OS cell growth. The p16INK4A gene was frequently deleted in many T‐cell lines, but not in HTLV‐1‐infected T‐cell lines. Taking these findings together, the functional inactivation of p16INK4A by Tax through protein‐protein interaction is suggested to contribute to cellular immortalization and transformation induced by HTLV‐1 infection.