title: A distinct role for Pin1 in the induction and maintenance of pluripotency.
abstract: 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.
authors.affiliation: Department of Microbiology, Yokohama City University School of Medicine, Kanazawa-ku, Yokohama, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Nishi
authors.forename: Hidenori
authors.initials: H
authors.lastname: Akutsu
authors.forename: Shinji
authors.initials: S
authors.lastname: Masui
authors.forename: Asami
authors.initials: A
authors.lastname: Kondo
authors.forename: Yoji
authors.initials: Y
authors.lastname: Nagashima
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kimura
authors.forename: Kilian
authors.initials: K
authors.lastname: Perrem
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shigeri
authors.forename: Masashi
authors.initials: M
authors.lastname: Toyoda
authors.forename: Akiko
authors.initials: A
authors.lastname: Okayama
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hirano
authors.forename: Akihiro
authors.initials: A
authors.lastname: Umezawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Sam W
authors.initials: SW
authors.lastname: Lee
authors.forename: Akihide
authors.initials: A
authors.lastname: Ryo
mesh_terms: D020816:Amino Acid Motifs; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase