Title of article :
Acetylation-Dependent Regulation of Skp2 Function
Author/Authors :
Hiroyuki Inuzuka، نويسنده , , Daming Gao، نويسنده , , Lydia W.S. Finley، نويسنده , , Wen Yang، نويسنده , , Lixin Wan، نويسنده , , Hidefumi Fukushima، نويسنده , , Y. Rebecca Chin، نويسنده , , Bo Zhai، نويسنده , , Shavali Shaik، نويسنده , , Alan W. Lau، نويسنده , , Zhiwei Wang، نويسنده , , Steven P. Gygi، نويسنده , , Keiko Nakayama، نويسنده , , Julie Teruya-Feldstein، نويسنده , , Alex Toker، نويسنده , , Marcia C. Haigis، نويسنده , , Pier Paolo Pandolfi، نويسنده , , Wenyi Wei، نويسنده ,
Issue Information :
هفته نامه با شماره پیاپی سال 2012
Pages :
15
From page :
179
To page :
193
Abstract :
Aberrant Skp2 signaling has been implicated as a driving event in tumorigenesis. Although the underlying molecular mechanisms remain elusive, cytoplasmic Skp2 correlates with more aggressive forms of breast and prostate cancers. Here, we report that Skp2 is acetylated by p300 at K68 and K71, which is a process that can be antagonized by the SIRT3 deacetylase. Inactivation of SIRT3 leads to elevated Skp2 acetylation, which leads to increased Skp2 stability through impairment of the Cdh1-mediated proteolysis pathway. As a result, Skp2 oncogenic function is increased, whereby cells expressing an acetylation-mimetic mutant display enhanced cellular proliferation and tumorigenesis in vivo. Moreover, acetylation of Skp2 in the nuclear localization signal (NLS) promotes its cytoplasmic retention, and cytoplasmic Skp2 enhances cellular migration through ubiquitination and destruction of E-cadherin. Thus, our study identifies an acetylation-dependent regulatory mechanism governing Skp2 oncogenic function and provides insight into how cytoplasmic Skp2 controls cellular migration.
Journal title :
CELL
Serial Year :
2012
Journal title :
CELL
Record number :
1021271
Link To Document :
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