Cytokine response gene 6 induces p21 and regulates both cell growth and arrest

Wen Fan, Gunther Richter, Anna Cereseto, Carol Beadling, Kendall A. Smith

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Cytokine response gene 6 (CR6), cloned from interleukin 2-stimulated T lymphocytes, is homologous to GADD45 and MyD118, genes which promote cell cycle arrest and apoptosis. To determine how this gene family could possibly mediate both cell survival/proliferation and cell cycle arrest/death, transfectants were generated so that the genes could be expressed ectopically, independently from their normal inducing agents. In cycling retinoblastoma protein-negative (pRb-) cells, ectopic CR6 expression blocked G2/M transition, but did not prevent G1/S transition so that endoreduplication resulted. By comparison, when CR6, GADD45, and MyD118 genes were expressed ectopically in proliferating pRb+ cells, either G1/S or G2/M transition was effectively blocked, so that there was no endoreduplication. Consistent with these findings, in proliferating pRb-cells, ectopic expression of CR6 promoted the expression of both G1 and G2/M cyclins. By comparison, in pRb+ cells, the expression of G1 cyclins was increased, while expression of the mitotic cyclins was decreased. However, in pRb+ cells, cyclin-dependent kinase activities associated with both G1 and G2/M cyclins were decreased. Moreover, ectopic expression of all three genes resulted in the expression of the CKI, p21, both in pRb- and pRb+ cells. The physiologic induction of CR6 expression by IL2 in quiescent normal human T cells occurs transiently in the first half of G1, coordinately with the expression of p21. Therefore, this gene family regulates G1 and G2, and promotes either cell growth or arrest by a common mechanism.

Original languageEnglish (US)
Pages (from-to)6573-6582
Number of pages10
JournalOncogene
Volume18
Issue number47
StatePublished - Nov 11 1999
Externally publishedYes

Fingerprint

Cytokines
Growth
Genes
Cyclin G2
Endoreduplication
Cell Cycle Checkpoints
Interleukin-2
Cyclin G1
T-Lymphocytes
Gene Expression
Retinoblastoma Protein
Cyclins
Cyclin-Dependent Kinases
Cell Survival
Cell Proliferation
Apoptosis

Keywords

  • Cell cycle
  • Cytokine
  • G1 and G2 progression

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Fan, W., Richter, G., Cereseto, A., Beadling, C., & Smith, K. A. (1999). Cytokine response gene 6 induces p21 and regulates both cell growth and arrest. Oncogene, 18(47), 6573-6582.

Cytokine response gene 6 induces p21 and regulates both cell growth and arrest. / Fan, Wen; Richter, Gunther; Cereseto, Anna; Beadling, Carol; Smith, Kendall A.

In: Oncogene, Vol. 18, No. 47, 11.11.1999, p. 6573-6582.

Research output: Contribution to journalArticle

Fan, W, Richter, G, Cereseto, A, Beadling, C & Smith, KA 1999, 'Cytokine response gene 6 induces p21 and regulates both cell growth and arrest', Oncogene, vol. 18, no. 47, pp. 6573-6582.
Fan W, Richter G, Cereseto A, Beadling C, Smith KA. Cytokine response gene 6 induces p21 and regulates both cell growth and arrest. Oncogene. 1999 Nov 11;18(47):6573-6582.
Fan, Wen ; Richter, Gunther ; Cereseto, Anna ; Beadling, Carol ; Smith, Kendall A. / Cytokine response gene 6 induces p21 and regulates both cell growth and arrest. In: Oncogene. 1999 ; Vol. 18, No. 47. pp. 6573-6582.
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