A Distinct Role for Pin1 in the Induction and Maintenance of Pluripotency

被引：51

作者：

Nishi, Mayuko

Akutsu, Hidenori ^{[4
]}

Masui, Shinji ^{[5
]}

Kondo, Asami

Nagashima, Yoji ^{[2
]}

Kimura, Hirokazu ^{[6
]}

Perrem, Kilian ^{[7
]}

Shigeri, Yasushi ^{[8
]}

Toyoda, Masashi ^{[4
]}

Okayama, Akiko ^{[3
]}

Hirano, Hisashi ^{[3
]}

Umezawa, Akihiro ^{[4
]}

Yamamoto, Naoki ^{[9
]}

Lee, Sam W. ^{[10
,11
]}

Ryo, Akihide ^{[1
]}

机构：

[1] Yokohama City Univ, Sch Med, Dept Microbiol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan

[2] Yokohama City Univ, Sch Med, Dept Pathol, Yokohama, Kanagawa 2360004, Japan

[3] Yokohama City Univ, Sch Med, Dept Supramol Biol, Yokohama, Kanagawa 2360004, Japan

[4] Natl Res Inst Child Hlth & Dev, Dept Reprod Biol, Tokyo 1578535, Japan

[5] Int Med Ctr Japan, Res Inst, Dept Regenerat Med, Tokyo 1628655, Japan

[6] Natl Inst Infect Dis, Infect Dis Surveillance Ctr, Tokyo 2080011, Japan

[7] Commonwealth Sci & Ind Res Org, Dickson, ACT 2602, Australia

[8] Natl Inst Adv Ind Sci & Technol, Osaka 5638577, Japan

[9] Natl Univ Singapore, Dept Microbiol, Singapore 117597, Singapore

[10] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA

[11] Harvard Univ, Sch Med, Charlestown, MA 02129 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2011年 / 286卷 / 13期

关键词：

EMBRYONIC STEM-CELLS; PROLYL ISOMERASE PIN1; SELF-RENEWAL; PHOSPHORYLATION; EXPRESSION; DIFFERENTIATION; ISOMERIZATION; SURVIVAL; MICE;

D O I：

10.1074/jbc.M110.187989

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

The prominent characteristics of pluripotent stem cells are their unique capacity to self-renew and pluripotency. Although pluripotent stem cell proliferation is maintained by specific intracellular phosphorylation signaling events, it has not been well characterized how the resulting phosphorylated proteins are subsequently regulated. We here report that the peptidylprolyl isomerase Pin1 is indispensable for the self-renewal and maintenance of pluripotent stem cells via the regulation of phosphorylated Oct4 and other substrates. Pin1 expression was found to be up-regulated upon the induction of induced pluripotent stem (iPS) cells, and the forced expression of Pin1 with defined reprogramming factors was observed to further enhance the frequency of iPS cell generation. The inhibition of Pin1 activity significantly suppressed colony formation and induced the aberrant differentiation of human iPS cells as well as murine ES cells. We further found that Pin1 interacts with the phosphorylated Ser(12)-Pro motif of Oct4 and that this in turn facilitates the stability and transcriptional activity functions of Oct4. Our current findings thus uncover an atypical role for Pin1 as a putative regulator of the induction and maintenance of pluripotency via the control of phosphorylation signaling. These data suggest that the manipulation of Pin1 function could be a potential strategy for the stable induction and proliferation of human iPS cells.

引用

页码：11593 / 11603

页数：11

共 35 条

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