Acetylation-dependent regulation of Skp2 function

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

137 Scopus Citations
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  • Hiroyuki Inuzuka
  • Daming Gao
  • Lydia W.S. Finley
  • Wen Yang
  • Lixin Wan
  • Hidefumi Fukushima
  • Bo Zhai
  • Shavali Shaik
  • Alan W. Lau
  • Zhiwei Wang
  • Steven P. Gygi
  • Keiko Nakayama
  • Julie Teruya-Feldstein
  • Alex Toker
  • Marcia C. Haigis
  • Pier Paolo Pandolfi
  • Wenyi Wei


Original languageEnglish
Pages (from-to)179-193
Journal / PublicationCell
Issue number1
Publication statusPublished - 6 Jul 2012
Externally publishedYes


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. © 2012 Elsevier Inc.

Citation Format(s)

Acetylation-dependent regulation of Skp2 function. / Inuzuka, Hiroyuki; Gao, Daming; Finley, Lydia W.S.; Yang, Wen; Wan, Lixin; Fukushima, Hidefumi; Chin, Y. Rebecca; Zhai, Bo; Shaik, Shavali; Lau, Alan W.; Wang, Zhiwei; Gygi, Steven P.; Nakayama, Keiko; Teruya-Feldstein, Julie; Toker, Alex; Haigis, Marcia C.; Pandolfi, Pier Paolo; Wei, Wenyi.

In: Cell, Vol. 150, No. 1, 06.07.2012, p. 179-193.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review