Human HTm4 is a hematopoietic cell cycle regulator

被引:32
作者
Donato, JL
Ko, J
Kutok, JL
Cheng, T
Shirakawa, T
Mao, XQ
Beach, D
Scadden, DT
Sayegh, MH
Adra, CN
机构
[1] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA
[2] Univ Wales Swansea, Expt Med Unit, Swansea, W Glam, Wales
[3] Kyoto Univ, Grad Sch Publ Hlth, Dept Hlth Promot & Human Behav, Kyoto, Japan
[4] RIKEN, SNP, Typing Ctr, Tokyo, Japan
[5] Genetica Inc, Cambridge, MA USA
[6] Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA USA
[7] Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Immunogenet & Transplantat, Boston, MA USA
[8] Harvard Univ, Sch Med, Childrens Hosp, Div Nephrol, Boston, MA USA
[9] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA
[10] Univ Pittsburgh, Dept Radiat Oncol, Pittsburgh, PA USA
[11] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA
关键词
D O I
10.1172/JCI200214025
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:51 / 58
页数:8
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