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Cell cycle‐dependent modifications in activities of pRb‐related tumor suppressors and proliferation‐specific CDP/ cut homeodomain factors in murine hematopoietic progenitor cells
Author(s) -
van Wijnen André 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.
Publication year - 1997
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19970915)66:4<512::aid-jcb10>3.0.co;2-d
Subject(s) - cell cycle , biology , e2f , microbiology and biotechnology , retinoblastoma protein , histone , cell growth , downregulation and upregulation , histone h4 , progenitor cell , cyclin dependent kinase , cyclin dependent kinase 1 , transcription factor , cancer research , stem cell , cell , gene , genetics
The histone H4 gene promoter provides a paradigm for defining transcriptional control operative at the G 1 /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 G 1 /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 upregulated at the G 1 /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. J. Cell. Biochem. 66:512–523, 1997. © 1997 Wiley‐Liss, Inc.