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.
journal_name
Cell Stem Celljournal_title
Cell stem cellauthors
Zou P,Yoshihara H,Hosokawa K,Tai I,Shinmyozu K,Tsukahara F,Maru Y,Nakayama K,Nakayama KI,Suda Tdoi
10.1016/j.stem.2011.07.003subject
Has Abstractpub_date
2011-09-02 00:00:00pages
247-61issue
3eissn
1934-5909issn
1875-9777pii
S1934-5909(11)00333-Xjournal_volume
9pub_type
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