Cell cycle-dependent modifications in activities of pRb-related tumor suppressors and proliferation-specific CDP/cut homeodomain factors in murine hematopoietic progenitor cells

Andre J van Wijnen, Cathleen Cooper, Paul Odgren, Farah Aziz, Antonio De Luca, Rauf A. Shakoori, Antonio Giordano, Peter J. Quesenberry, Jane B. Lian, Gary S. Stein, Janet L. Stein

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

The histone H4 gene promoter provides a paradigm for defining transcriptional control operative at the G1/S phase transition point in the cell cycle. Transcription of the cell cycle-dependent histone H4 gene is upregulated at the onset of S phase, and the cell cycle control element that mediates this activation has been functionally mapped to a proximal promoter domain designated Site II. Activity of Site II is regulated by an E2F- independent mechanism involving binding of the oncoprotein IRF2 and the multisubunit protein HiNF-D, which contains the homeodomain CDP/cut, CDC2, cyclin A, and the tumor suppressor pRb. To address mechanisms that define interactions of Site II regulatory factors with this cell cycle control element, we have investigated these determinants of transcriptional regulation at the G1/S phase transition in FDC-P1 hematopoietic progenitor cells. The representation and activities of histone gene regulatory factors were examined as a function of FDC-P1 growth stimulation. We find striking differences in expression of the pRb-related growth regulatory proteins (pRb/p105, pRb2/p130, and p107) following the onset of proliferation. pRb2/p130 is present at elevated levels in quiescent cells and declines following growth stimulation. By contrast, pRb and p107 are minimally represented in quiescent FDC-P1 cells but are opregulated at the G1/S phase transition point. We also observe a dramatic upregulation of the cellular levels of pRb2/p130-associated protein kinase activity when S phase is initiated. Selective interactions of pRb and p107 with CDP/cut are observed during the FDC-P1 cell cycle and suggest functional linkage to competency for DNA binding and/or transcriptional activity. These results are particularly significant in the context of hematopoietic differentiation where stringent control of the cell cycle program is requisite for expanding the stem cell population during development and tissue renewal.

Original languageEnglish (US)
Pages (from-to)512-523
Number of pages12
JournalJournal of Cellular Biochemistry
Volume66
Issue number4
DOIs
StatePublished - Sep 15 1997
Externally publishedYes

Fingerprint

Cytidine Diphosphate
Hematopoietic Stem Cells
S Phase
Tumors
Cell Cycle
Cells
Phase Transition
G1 Phase
Cell Cycle Checkpoints
Histones
Neoplasms
Genes
Phase transitions
Growth
Cyclin A
Oncogene Proteins
Regulator Genes
Protein Kinases
Transcription
Stem cells

Keywords

  • CDP/cut
  • Cell cycle control
  • G/S phase transition point
  • H4 gene promoter
  • Interferon regulatory factor 2

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Cell cycle-dependent modifications in activities of pRb-related tumor suppressors and proliferation-specific CDP/cut homeodomain factors in murine hematopoietic progenitor cells. / van Wijnen, Andre J; Cooper, Cathleen; Odgren, Paul; Aziz, Farah; De Luca, Antonio; Shakoori, Rauf A.; Giordano, Antonio; Quesenberry, Peter J.; Lian, Jane B.; Stein, Gary S.; Stein, Janet L.

In: Journal of Cellular Biochemistry, Vol. 66, No. 4, 15.09.1997, p. 512-523.

Research output: Contribution to journalArticle

van Wijnen, Andre J ; Cooper, Cathleen ; Odgren, Paul ; Aziz, Farah ; De Luca, Antonio ; Shakoori, Rauf A. ; Giordano, Antonio ; Quesenberry, Peter J. ; Lian, Jane B. ; Stein, Gary S. ; Stein, Janet L. / Cell cycle-dependent modifications in activities of pRb-related tumor suppressors and proliferation-specific CDP/cut homeodomain factors in murine hematopoietic progenitor cells. In: Journal of Cellular Biochemistry. 1997 ; Vol. 66, No. 4. pp. 512-523.
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AU - Aziz, Farah

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AU - Giordano, Antonio

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