Complex regulation of CDK2 during phorbol ester-induced hematopoietic differentiation

Clement Asiedu, Joseph Biggs, Andrew Kraft

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Phorbol myristate acetate (PMA) treatment of U937 human leukemic cells results in late G1 cell cycle arrest and terminal monocyte/macrophage-like differentiation. The PMA-induced G1 arrest involves a marked decrease in cdk2 activity, which correlates with total cdk2 dephosphorylation. Here, we show that the levels of cyclin A mRNA and protein markedly decrease during PMA- induced differentiation of U937 cells. In contrast, the level of cyclin E protein remains unchanged and in a complex with cdk2 during the entire course of PMA treatment. During the PMA-induced differentiation, cyclin E-associated cdk2 activity drops markedly. Furthermore, the amount of p27(Kip1) protein associated with cyclin E/cdk2 greatly increased 24 to 72 hours after PMA treatment. The absence of changes in p27(Kip1) mRNA levels by Northern blot suggest that the levels of this protein are controlled by posttranscriptional or posttranslational mechanism(s). These results show that the mechanisms mediating PMA-induced G1 arrest the complex. The inhibition of cdk2 activity is associated with (1) a decrease in cyclin A protein levels, (2) inactivation of cdk2 complexes, and (3) upregulation of p27(Kip1) protein.

Original languageEnglish (US)
Pages (from-to)3430-3437
Number of pages8
JournalBlood
Volume90
Issue number9
StatePublished - 1997
Externally publishedYes

Fingerprint

Phorbol Esters
Tetradecanoylphorbol Acetate
Cyclin E
Cyclin-Dependent Kinase Inhibitor p27
Cyclin A
Proteins
G1 Phase Cell Cycle Checkpoints
U937 Cells
Messenger RNA
Macrophages
Northern Blotting
Monocytes
Up-Regulation
Cells

ASJC Scopus subject areas

  • Hematology

Cite this

Complex regulation of CDK2 during phorbol ester-induced hematopoietic differentiation. / Asiedu, Clement; Biggs, Joseph; Kraft, Andrew.

In: Blood, Vol. 90, No. 9, 1997, p. 3430-3437.

Research output: Contribution to journalArticle

Asiedu, Clement ; Biggs, Joseph ; Kraft, Andrew. / Complex regulation of CDK2 during phorbol ester-induced hematopoietic differentiation. In: Blood. 1997 ; Vol. 90, No. 9. pp. 3430-3437.
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