Cyclin A1, the alternative A-type cyclin, contributes to G1/S cell cycle progression in somatic cells

Ping Ji, Shuchi Agrawal, Sven Diederichs, Nicole Bäumer, Annette Becker, Thomas Cauvet, Sascha Kowski, Carmela Beger, Karl Welte, Wolfgang E. Berdel, Hubert Serve, Carsten Müller-Tidow

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Cyclin A1 is an alternative A-type cyclin that is essential for spermatogenesis, but it is also expressed in hematopoietic progenitor cells and in acute myeloid leukemia. Its functions during cell cycle progression of somatic cells are incompletely understood. Here, we have analysed the cell cycle functions of cyclin A1 in transformed and non-transformed cells. Murine embryonic fibroblasts derived from cyclin A1-deficient mice were significantly impaired in their proliferative capacity. In accordance, cyclin A1-/- cells accumulated in G1 and G2/M phase while the percentage of S phase cells decreased. Also, lectin stimulated splenic lymphocytes from cyclin A1 -/- mice proliferated slower than their wild-type counterparts. Forced cyclin A1 overexpression in NIH3T3 cells and in U937 leukemic cells either by transient transfection or by retroviral infection enhanced S phase entry. Consequently, siRNA mediated silencing of cyclin A1 in highly cyclin A1 expressing ML1 leukemic cells significantly slowed S phase entry, decreased proliferation and inhibited colony formation. Taken together, these analyses demonstrate that cyclin A1 contributes to G1 to S cell cycle progression in somatic cells. Cyclin A1 overexpression enhances S phase entry consistent with an oncogenic function. Finally, cyclin A1 might be a therapeutic target since its silencing inhibited leukemia cell growth.

Original languageEnglish (US)
Pages (from-to)2739-2744
Number of pages6
JournalOncogene
Volume24
Issue number16
DOIs
StatePublished - Apr 14 2005
Externally publishedYes

Keywords

  • Cell cycle
  • Cyclin A1
  • Leukemia
  • siRNA

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Ji, P., Agrawal, S., Diederichs, S., Bäumer, N., Becker, A., Cauvet, T., Kowski, S., Beger, C., Welte, K., Berdel, W. E., Serve, H., & Müller-Tidow, C. (2005). Cyclin A1, the alternative A-type cyclin, contributes to G1/S cell cycle progression in somatic cells. Oncogene, 24(16), 2739-2744. https://doi.org/10.1038/sj.onc.1208356