The prolyl isomerase Pin1 stabilizes the human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein and promotes malignant transformation

被引:39
作者
Jeong, Soo-Jin [1 ]
Ryo, Akihide [1 ]
Yamamoto, Naoki [1 ]
机构
[1] Natl Inst Infect Dis, AIDS Res Ctr, Shinjuku Ku, Tokyo 1628640, Japan
关键词
Pin1; Tax; Protein stability; Ubiquitination; Transformation; I TAX; PROTEIN; UBIQUITINATION; DEGRADATION; INHIBITION; APOPTOSIS; P53;
D O I
10.1016/j.bbrc.2009.02.024
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:294 / 299
页数:6
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