Human HTm4 is a hematopoietic cell cycle regulator

J Clin Invest. 2002 Jan;109(1):51-8. doi: 10.1172/JCI14025.


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 types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • CDC2-CDC28 Kinases*
  • Cell Cycle / physiology*
  • Cell Cycle Proteins*
  • Cells, Cultured
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase Inhibitor Proteins
  • Cyclin-Dependent Kinases / metabolism
  • Dual-Specificity Phosphatases
  • Gene Expression Regulation
  • Hematopoiesis / physiology*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / physiology
  • Humans
  • Immunohistochemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Protein Serine-Threonine Kinases / metabolism
  • Protein Tyrosine Phosphatases / metabolism
  • Transfection
  • Two-Hybrid System Techniques


  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor Proteins
  • MS4A3 protein, human
  • Membrane Proteins
  • Protein Serine-Threonine Kinases
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases
  • CDKN3 protein, human
  • Dual-Specificity Phosphatases
  • Protein Tyrosine Phosphatases