The HTLV Tax protein is Crucial for viral replication and malignant transformation. We investigated the possible role of peptidyl prolyl isomerase Pin1 in the positive regulation of the human T-cell leukemia virus type 1 Tax. Pin1 is highly expressed in adult T-cell leukemia (ATL) cells expressing Tax protein and forced expression of Pin1 in turn increases the Tax protein expression. Pin1 prolonged the protein half-life of Tax by suppressing the ubiquitination and subsequent lysosomal degradation of Tax. Pin1 interacts with phosphorylated Tax on its Ser160-Pro motif at the mitotic phase. Finally, we found that Pin1 plays a supporting role in Tax-mediated cell transformation. Our current study demonstrates an important role for Pin1 in the post-translational regulation of Tax and suggests that the targeting of Pin1 may offer a new insight into the pathogenesis of HTLV-I related diseases. (c) 2009 Elsevier Inc. All rights reserved.