P57 Kip2 and p27 Kip1 cooperate to maintain hematopoietic stem cell quiescence through interactions with Hsc70

Peng Zou, Hiroki Yoshihara, Kentaro Hosokawa, Ikue Tai, Kaori Shinmyozu, Fujiko Tsukahara, Yoshiro Maru, Keiko Nakayama, Keiichi I. Nakayama, Toshio Suda

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169 Citations (Scopus)

Abstract

Cell cycle regulators play critical roles in the balance between hematopoietic stem cell (HSC) dormancy and proliferation. In this study, we report that cell cycle entry proceeded normally in HSCs null for cyclin-dependent kinase (CDK) inhibitor p57 due to compensatory upregulation of p27. HSCs null for both p57 and p27, however, were more proliferative and had reduced capacity to engraft in transplantation. We found that heat shock cognate protein 70 (Hsc70) interacts with both p57 and p27 and that the subcellular localization of Hsc70 was critical to maintain HSC cell cycle kinetics. Combined deficiency of p57 and p27 in HSCs resulted in nuclear import of an Hsc70/cyclin D1 complex, concomitant with Rb phosphorylation, and elicited severe defects in maintaining HSC quiescence. Taken together, these data suggest that regulation of cytoplasmic localization of Hsc70/cyclin D1 complex by p57 and p27 is a key intracellular mechanism in controlling HSC dormancy.

Original languageEnglish
Pages (from-to)247-261
Number of pages15
JournalCell stem cell
Volume9
Issue number3
DOIs
Publication statusPublished - 2011 Sep 2

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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    Zou, P., Yoshihara, H., Hosokawa, K., Tai, I., Shinmyozu, K., Tsukahara, F., Maru, Y., Nakayama, K., Nakayama, K. I., & Suda, T. (2011). P57 Kip2 and p27 Kip1 cooperate to maintain hematopoietic stem cell quiescence through interactions with Hsc70. Cell stem cell, 9(3), 247-261. https://doi.org/10.1016/j.stem.2011.07.003