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Regulation of p21(WAF1) Expression During Normal Myeloid
Differentiation
Richard A. Steinman,
Jianping Huang,
Beatrice Yaroslavskiy,
Julie
P. Goff,
Edward D. Ball, and
Aline Nguyen
From the University of Pittsburgh Cancer Institute and Departments of
Medicine and Radiation Oncology, University of Pittsburgh School of
Medicine, Pittsburgh, PA.
The G1-phase cell-cycle inhibitor p21 has been proposed to mediate
growth arrest during differentiation. Upregulation of p21 has been
shown in multiple cell lines induced to differentiate; however, the
mechanism of p21 induction during normal differentiation is largely
unknown. In this report, we use normal hematopoietic precursor cells
obtained from umbilical cord to model p21 regulation during
differentiation. Myeloid maturation of CD34+ precursor
cells is associated with a marked increase in p21 expression at the RNA
and protein level. The upregulation of p21 transcripts during
differentiation is associated with decreased binding to a highly
conserved 44-bp fragment within the p21 promoter. This 44-bp regulatory
element binds a novel modulator of p21 expression. It is of
considerable interest that, although the binding activity is expressed
in p53-negative as well as in p53-positive cells, the DNA sequence
recognized by this protein overlaps a PuPuPuC(A/T)(T/A)GPyPyPy consensus sequence for p53.
Blood, Vol. 91 No. 12 (June 15), 1998:
pp. 4531-4542
© 1998 by The American Society of Hematology.
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