CDK6 blocks differentiation: Coupling cell proliferation to the block to differentiation in leukemic cells

Igor Matushansky, Farshid Radparvar, Arthur I. Skoultchi

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Cell proliferation and differentiation are highly coordinated during normal development. Many tumor cells exhibit both uncontrolled proliferation and a block to terminal differentiation. To understand the mechanisms coordinating these two processes, we have investigated the relation between cyclin-dependent kinase (CDK) activities and the block to differentiation in murine erythroleukemia (MEL) cells. We found that CDK6 (but not CDK4) is rapidly downregulated as MEL cells are induced to reenter erythroid differentiation and that maintenance of CDK6 (but not CDK4) activity by transfection blocks differentiation. Moreover, we found that PU.1, an Ets transcription factor that is oncogenic in erythroid cells and also can block their differentiation, controls the synthesis of CDK6 mRNA. These results suggest a mechanism for coupling proliferation and the block to differentiation in these leukemic cells through the action of an oncogenic transcription factor (PU.1) on a key cell cycle regulator (CDK6). Our findings suggest that studying the relative roles of CDK6 and CDK4 in other types of malignant cells will be important in designing approaches for cell cycle inhibition and differentiation therapy in cancer.

Original languageEnglish (US)
Pages (from-to)4143-4149
Number of pages7
JournalOncogene
Volume22
Issue number27
DOIs
StatePublished - Jul 3 2003

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Cell Proliferation
Leukemia, Erythroblastic, Acute
Cell Differentiation
Cell Cycle
Proto-Oncogene Proteins c-ets
Erythroid Cells
Cyclin-Dependent Kinases
Transfection
Neoplasms
Down-Regulation
Maintenance
Messenger RNA
Therapeutics

Keywords

  • Cyclin-dependent kinase 6
  • Differentiation
  • Erythroleukemia
  • Proliferation
  • PU.1

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

CDK6 blocks differentiation : Coupling cell proliferation to the block to differentiation in leukemic cells. / Matushansky, Igor; Radparvar, Farshid; Skoultchi, Arthur I.

In: Oncogene, Vol. 22, No. 27, 03.07.2003, p. 4143-4149.

Research output: Contribution to journalArticle

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