Cyclin G2 is up-regulated during growth inhibition and B cell antigen receptor-mediated cell cycle arrest

Mary C Horne, Karen L. Donaldson, Gay Lynn Goolsby, David Tran, Michael Mulheisen, Johannes W Hell, Alan F. Wahl

Research output: Contribution to journalArticle

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Abstract

Human cyclin G2 together with its closest homolog cyclin G1 defines a novel family of cyclins (Horne, M. C., Goolsby, G. L., Donaldson, K. L., Tran, D., Neubauer, M., and Wahl, A. F. (1996) J. Biol. Chem. 271, 6050- 6061). Cyclin G2 is highly expressed in the immune system where immunologic tolerance subjects self-reactive lymphocytes to negative selection and clonal deletion via apoptosis. Here we investigated the effect of growth inhibitory signals on cyclin G2 mRNA abundance in different maturation stage-specific murine B cell lines. Upon treatment of wild-type and p53 null B cell lines with the negative growth factor, transforming growth factor β1, or the growth inhibitory corticosteroid dexamethasone, cyclin G2 mRNA levels were increased in a time-dependent manner 5-14-fold over control cell levels. Unstimulated immature B cell lines (WEHI-231 and CH31) and unstimulated or IgM B cell receptor (BCR)-stimulated mature B cell lines (BAL-17 and CH12) rapidly proliferate and express low levels of cyclin G2 mRNA. In contrast, BCR-stimulated immature B cell lines undergo growth arrest and coincidentally exhibit an ~10-fold increase in cyclin G2 transcripts and a decrease in cyclin D2 message. Costimulation of WEHI-231 and CH31 cells with calcium ionophores and protein kinase C agonists partially mimics anti-IgM stimulation and elicits a strong up-regulation of cyclin G2 mRNA and down- regulation of cyclin D2 mRNA. Signaling mutants of WEHI-231 that are deficient in the phosphoinositide signaling pathway and consequently resistant to the BCR stimulus-induced growth arrest did not display a significant increase in cyclin G2 or decrease in cyclin D2 mRNAs when challenged with anti-IgM antibodies. The two polyclonal activators lipopolysaccharide and soluble gp30, which inhibit the growth arrest response of immature B cells, suppressed cyclin G2 mRNA expression induced by BCR stimulation. These results suggest that in murine B cells responding to growth inhibitory stimuli cyclin G2 may be a key negative regulator of cell cycle progression.

Original languageEnglish (US)
Pages (from-to)12650-12661
Number of pages12
JournalJournal of Biological Chemistry
Volume272
Issue number19
DOIs
StatePublished - May 9 1997
Externally publishedYes

Fingerprint

Cyclin G2
B-Cell Antigen Receptors
Cell Cycle Checkpoints
Cells
B-Lymphocytes
Growth
Cyclin D2
Messenger RNA
B-Lymphoid Precursor Cells
Cell Line
Cyclin G1
Clonal Deletion
Dimercaprol
Null Lymphocytes
Cyclins
Lymphocytes
Calcium Ionophores
Immune system
Transforming Growth Factors
Phosphatidylinositols

ASJC Scopus subject areas

  • Biochemistry

Cite this

Cyclin G2 is up-regulated during growth inhibition and B cell antigen receptor-mediated cell cycle arrest. / Horne, Mary C; Donaldson, Karen L.; Goolsby, Gay Lynn; Tran, David; Mulheisen, Michael; Hell, Johannes W; Wahl, Alan F.

In: Journal of Biological Chemistry, Vol. 272, No. 19, 09.05.1997, p. 12650-12661.

Research output: Contribution to journalArticle

Horne, Mary C ; Donaldson, Karen L. ; Goolsby, Gay Lynn ; Tran, David ; Mulheisen, Michael ; Hell, Johannes W ; Wahl, Alan F. / Cyclin G2 is up-regulated during growth inhibition and B cell antigen receptor-mediated cell cycle arrest. In: Journal of Biological Chemistry. 1997 ; Vol. 272, No. 19. pp. 12650-12661.
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AU - Hell, Johannes W

AU - Wahl, Alan F.

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