Ablation of G(o)α overrides G1 restriction point control through Ras/ERK/cyclin D1-CDK activities

Jason D. Weber, Jie Cheng, Daniel Max Raben, Alice Gardner, Joseph J. Baldassare

Research output: Contribution to journalArticle

Abstract

We have generated stable IIC9 cell lines, Goa1 and Goa2, that overexpress full-length antisense G(o)α RNA. As shown previously, expression of antisense G(o)α RNA ablated the a subunit of the heterotrimeric G protein, G(o), resulting in growth in the absence of mitogen. To better understand this change in IIC9 phenotype, we have characterized the signaling pathway and cell cycle events previously shown to be important in control of IIC9 G1/S phase progression. In this paper we clearly demonstrate that ablation of G(o)α results in growth, constitutively active Ras/ERK, elevated expression of cyclin D1, and constitutively active cyclin D1-CDK complexes, all in the absence of mitogen. Furthermore, these characteristics were abolished by the transient overexpression of the transducin heterotrimeric G protein α subunit strongly suggesting the transformation of G(o)α-ablated cells involves G(o)βγ subunits. This is the (first study to implicate a heterotrimeric G protein in tumor suppression.

Original languageEnglish (US)
Pages (from-to)17320-17326
Number of pages7
JournalJournal of Biological Chemistry
Volume272
Issue number28
DOIs
StatePublished - 1997

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G1 Phase Cell Cycle Checkpoints
Heterotrimeric GTP-Binding Proteins
Cyclin D1
Ablation
Mitogens
Cells
RNA
Transducin
Gastrin-Secreting Cells
Protein Subunits
G1 Phase
Growth
S Phase
Tumors
Cell Cycle
Phenotype
Cell Line
Neoplasms

ASJC Scopus subject areas

  • Biochemistry

Cite this

Ablation of G(o)α overrides G1 restriction point control through Ras/ERK/cyclin D1-CDK activities. / Weber, Jason D.; Cheng, Jie; Raben, Daniel Max; Gardner, Alice; Baldassare, Joseph J.

In: Journal of Biological Chemistry, Vol. 272, No. 28, 1997, p. 17320-17326.

Research output: Contribution to journalArticle

Weber, Jason D. ; Cheng, Jie ; Raben, Daniel Max ; Gardner, Alice ; Baldassare, Joseph J. / Ablation of G(o)α overrides G1 restriction point control through Ras/ERK/cyclin D1-CDK activities. In: Journal of Biological Chemistry. 1997 ; Vol. 272, No. 28. pp. 17320-17326.
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