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- Title
Granulocytic differentiation of myeloid progenitor cells by p130, the retinoblastoma tumor suppressor homologue.
- Authors
Mori, Akio; Higashi, Hideaki; Hoshikawa, Yutaka; Imamura, Masahiro; Asaka, Masahiro; Hatakeyama, Masanori
- Abstract
The retinoblastoma protein (pRB) and the related pocket proteins, p107 and p130, play crucial roles in mammalian cell cycle control. Recent studies indicate that these pocket proteins are also involved in cellular differentiation processes. We demonstrate in this work that the pRB-related p130 selectively accumulates during the in vitro differentiation of the myeloid progenitor cell, 32Dcl3, into granulocyte in response to granulocyte-colony stimulating factor (G-CSF). This G-CSF-dependent granulocytic differentiation is blocked by the adenovirus E1A oncoprotein, which binds to and inactivates the pRB family of pocket proteins including p130. Furthermore, enforced overexpression of p130 but not pRB inhibits the myeloid cell proliferation that is concomitantly associated with granulocytic differentiation morphologically characterized by nuclear segmentation. However, simple G1-cell cycle arrest induced by cytokine deprivation or ectopic overexpression of the p27 cyclin-dependent kinase inhibitor, or inhibition of E2F activities by dominant negative DP-1 is not sufficient to trigger granulocytic differentiation. The differentiation-promoting activity of p130 in myeloid cells requires both the pocket domain and the spacer domain. Our results indicate that the pRB-related p130 plays a critical role in myeloid cell differentiation and suggest that coupling of cell cycle exit with the cellular differentiation program may be specifically achieved by p130.
- Subjects
RETINOBLASTOMA; TUMOR suppressor genes; CELL differentiation; CELL cycle; CELL proliferation
- Publication
Oncogene, 1999, Vol 18, Issue 46, p6209
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1203044