The prolyl isomerase Pin1 stabilizes the human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein and promotes malignant transformation
The prolyl isomerase Pin1 stabilizes the human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein and promotes malignant transformation
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DOI：
10.1016/j.bbrc.2009.02.024
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发表时间：
2009-04-03
影响因子：
3.1
通讯作者：
Yamamoto, Naoki
中科院分区：
文献类型：
--
作者：
Jeong, Soo-Jin;Ryo, Akihide;Yamamoto, Naoki
HTLV Tax蛋白对病毒复制和恶性转化至关重要。我们研究了肽基脯氨酰异构酶Pin 1在人类T细胞白血病病毒1型Tax正调控中的可能作用。Pin 1在表达Tax蛋白的成人T细胞白血病（ATL）细胞中高度表达，并且Pin 1的强制表达反过来增加Tax蛋白的表达。Pin 1通过抑制Tax的泛素化和随后的溶酶体降解来延长Tax的蛋白半衰期。Pin 1在有丝分裂期与其Ser 160-Pro基序上的磷酸化Tax相互作用。最后，我们发现Pin 1在Tax介导的细胞转化中起支持作用。我们目前的研究表明Pin 1在Tax的翻译后调节中发挥重要作用，并表明Pin 1的靶向可能为HTLV-I相关疾病的发病机制提供新的见解。(c)2009 Elsevier Inc. All rights reserved.
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.