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- Title
Human HTm4 is a hematopoietic cell cycle regulator.
- Authors
Donato, José L; Ko, Jon; Kutok, Jeffery L; Cheng, Tao; Shirakawa, Taro; Mao, Xiao-Quan; Beach, David; Scadden, David T; Sayegh, Mohamed H; Adra, Chaker N
- Abstract
Proper control of cell cycle progression is critical for the constant self-renewal, differentiation, and homeostasis of the hematopoietic system. Cells of all types share the common cell cycle regulators. The different expression patterns of common regulators, in a broad sense, define cell-type or lineage specificity. However, there remains the possibility of hematopoietic cell cycle regulators tailored to the demands of the hematopoietic system. Here we describe a novel protein, HTm4, which serves as a hematopoietic cell cycle regulator. Our data indicate that HTm4 is expressed in hematopoietic tissues and is tightly regulated during the differentiation of hematopoietic stem cells. It binds to cyclin-dependent kinase-associated (CDK-associated) phosphatase-CDK2 (KAP-CDK2) complexes, and the three proteins demonstrate similar patterns of cellular expression in human lymphoid tissues. HTm4 stimulates the phosphatase activity of KAP, and its C-terminal region is required for binding to KAP-CDK2 complexes and the modulation of KAP activity. Overexpression of HTm4 can cause cell cycle arrest at the G(0)/G(1) phase. Thus, HTm4 is a novel hematopoietic modulator for the G(1)-S cell cycle transition.
- Publication
The Journal of clinical investigation, 2002, Vol 109, Issue 1, p51
- ISSN
0021-9738
- Publication type
Journal Article
- DOI
10.1172/JCI14025