HTLV-1 Tax protein interacts with cyclin-dependent kinase inhibitor p16Ink4a and counteracts its inhibitory activity to CDK4.

Suzuki, Takeshi; Yoshida, Mitsuaki

Tax, a regulatory protein of HTLV-1, is an oncoprotein which immortalizes human T-cells and induces tumors in transgenic mice. Here, we found that Tax binds to a cyclin-dependent kinase inhibitor, p161nk4a, p161nk4a binds to cyclin-dependent kinases, CDK4 and CDK6, and inhibits their activity, resulting in suppression of G1 phase progression. The binding of Tax to p161nk4a induced a reduction of p161nk4a/CDK4 complex, with subsequent activation of CDK4 kinase. Tax also suppressed p161nk4amediated inhibition of cell growth. The p161nk4a 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 p161nk4a by Tax through protein-protein interaction is suggested to contribute to cellular immortalization and transformation by HTLV-1.

HTLV-I; PROTEINS; CYCLIN-dependent kinases; TRANSGENIC mice; LABORATORY mice; CELL lines; PROTEIN-protein interactions

Leukemia (08876924), 1997, Vol 11, p14

0887-6924

Academic Journal