Human HTm4 is a hematopoietic cell cycle regulator
José L. Donato, … , Mohamed H. Sayegh, Chaker N. Adra
José L. Donato, … , Mohamed H. Sayegh, Chaker N. Adra
Published January 1, 2002
Citation Information: J Clin Invest. 2002;109(1):51-58. https://doi.org/10.1172/JCI14025.
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Article

Human HTm4 is a hematopoietic cell cycle regulator

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 G0/G1 phase. Thus, HTm4 is a novel hematopoietic modulator for the G1-S cell cycle transition.

Authors

José L. Donato, Jon Ko, Jeffery L. Kutok, Tao Cheng, Taro Shirakawa, Xiao-Quan Mao, David Beach, David T. Scadden, Mohamed H. Sayegh, Chaker N. Adra

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Figure 3

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(a) Colocalization of HTm4 and KAP. Staining was visualized with goat an...
(a) Colocalization of HTm4 and KAP. Staining was visualized with goat anti-mouse IgG Texas Red–conjugated (left) or goat anti-rabbit IgG FITC–conjugated (middle) secondary Ab’s. Merged image is given on the right showing that HTm4 and KAP colocalized predominately in the perinuclear area. (b) HTm4 is located in the intracellular membrane fraction. Source of the samples are denoted on the top row. Samples shown are in duplicates. The presence of HTm4 is indicated on the right after Western blot analysis. (c) Staining of U937 with anti-HTm4 Ab. The manipulations of samples are denoted on the top. The filled peaks represent the staining with anti-HTm4, and the open peaks represent IgG control. x axis, cell counts; y axis, signal intensity of FITC fluorescence. Representative figures of at least five experiments.