TY - JOUR
T1 - PU.1 directly regulates cdk6 gene expression, linking the cell proliferation and differentiation programs in erythroid cells
AU - Choe, Kevin S.
AU - Ujhelly, Olga
AU - Wontakal, Sandeep N.
AU - Skoultchi, Arthur I.
PY - 2010/1/29
Y1 - 2010/1/29
N2 - Cell proliferation and differentiation are highly coordinated processes during normal development. Most leukemia cells are blocked from undergoing terminal differentiation and also exhibit uncontrolled proliferation. Dysregulated expression of transcription factor PU.1 is strongly associated with Friend virus-induced erythroleukemia. PU.1 inhibits erythroid differentiation by binding to and inhibiting GATA-1. PU.1 also may be involved in controlling proliferation of erythroid cells. We reported previously that the G1 phase-specific cyclin-dependent kinase 6 (CDK6) also blocks erythroid differentiation. We now report that PU.1 directly stimulates transcription of the cdk6 gene in both normal erythroid progenitors and erythroleukemia cells, as well as in macrophages. We propose that PU.1 coordinates proliferation and differentiation in immature erythroid cells by inhibiting the GATA-1-mediated gene expression program and also by regulating expression of genes that control progression through the G1 phase of the cell cycle, the period during which the decision to differentiate is made.
AB - Cell proliferation and differentiation are highly coordinated processes during normal development. Most leukemia cells are blocked from undergoing terminal differentiation and also exhibit uncontrolled proliferation. Dysregulated expression of transcription factor PU.1 is strongly associated with Friend virus-induced erythroleukemia. PU.1 inhibits erythroid differentiation by binding to and inhibiting GATA-1. PU.1 also may be involved in controlling proliferation of erythroid cells. We reported previously that the G1 phase-specific cyclin-dependent kinase 6 (CDK6) also blocks erythroid differentiation. We now report that PU.1 directly stimulates transcription of the cdk6 gene in both normal erythroid progenitors and erythroleukemia cells, as well as in macrophages. We propose that PU.1 coordinates proliferation and differentiation in immature erythroid cells by inhibiting the GATA-1-mediated gene expression program and also by regulating expression of genes that control progression through the G1 phase of the cell cycle, the period during which the decision to differentiate is made.
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U2 - 10.1074/jbc.M109.077727
DO - 10.1074/jbc.M109.077727
M3 - Article
C2 - 19955566
AN - SCOPUS:77449092637
SN - 0021-9258
VL - 285
SP - 3044
EP - 3052
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 5
ER -