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Absence of the CAAX endoprotease Rce1: effects on cell growth and transformation.

Publication ,  Journal Article
Bergo, MO; Ambroziak, P; Gregory, C; George, A; Otto, JC; Kim, E; Nagase, H; Casey, PJ; Balmain, A; Young, SG
Published in: Mol Cell Biol
January 2002

After isoprenylation, the Ras proteins and other CAAX proteins undergo two additional enzymatic modifications-endoproteolytic release of the last three amino acids of the protein by the protease Rce1 and methylation of the carboxyl-terminal isoprenylcysteine by the methyltransferase Icmt. This postisoprenylation processing is thought to be important for the association of Ras proteins with membranes. Blocking postisoprenylation processing, by inhibiting Rce1, has been suggested as a potential approach for retarding cell growth and blocking cellular transformation. The objective of this study was to develop a cell culture system for addressing these issues. We generated mice with a conditional Rce1 allele (Rce1(flox)) and produced Rce1(flox/flox) fibroblasts. Cre-mediated excision of Rce1 (thereby producing Rce1(Delta/Delta) fibroblasts) eliminated Ras endoproteolytic processing and methylation and caused a partial mislocalization of truncated K-Ras and H-Ras fusion proteins within cells. Rce1(Delta/Delta) fibroblasts grew more slowly than Rce1(flox/flox) fibroblasts. The excision of Rce1 also reduced Ras-induced transformation, as judged by the growth of colonies in soft agar. The excision of Rce1 from a Rce1(flox/flox) skin carcinoma cell line also significantly retarded the growth of cells, and this effect was exaggerated by cotreatment of the cells with a farnesyltransferase inhibitor. These studies support the idea that interference with postisoprenylation processing retards cell growth, limits Ras-induced transformation, and sensitizes tumor cells to a farnesyltransferase inhibitor.

Duke Scholars

Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

January 2002

Volume

22

Issue

1

Start / End Page

171 / 181

Location

United States

Related Subject Headings

  • ras Proteins
  • Tumor Cells, Cultured
  • Transfection
  • Skin Neoplasms
  • Protein Processing, Post-Translational
  • Microscopy, Confocal
  • Mice, Nude
  • Mice
  • Humans
  • Genes, ras
 

Citation

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MLA
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Bergo, M. O., Ambroziak, P., Gregory, C., George, A., Otto, J. C., Kim, E., … Young, S. G. (2002). Absence of the CAAX endoprotease Rce1: effects on cell growth and transformation. Mol Cell Biol, 22(1), 171–181. https://doi.org/10.1128/MCB.22.1.171-181.2002
Bergo, Martin O., Patricia Ambroziak, Cria Gregory, Amanda George, James C. Otto, Edward Kim, Hiroki Nagase, Patrick J. Casey, Allan Balmain, and Stephen G. Young. “Absence of the CAAX endoprotease Rce1: effects on cell growth and transformation.Mol Cell Biol 22, no. 1 (January 2002): 171–81. https://doi.org/10.1128/MCB.22.1.171-181.2002.
Bergo MO, Ambroziak P, Gregory C, George A, Otto JC, Kim E, et al. Absence of the CAAX endoprotease Rce1: effects on cell growth and transformation. Mol Cell Biol. 2002 Jan;22(1):171–81.
Bergo, Martin O., et al. “Absence of the CAAX endoprotease Rce1: effects on cell growth and transformation.Mol Cell Biol, vol. 22, no. 1, Jan. 2002, pp. 171–81. Pubmed, doi:10.1128/MCB.22.1.171-181.2002.
Bergo MO, Ambroziak P, Gregory C, George A, Otto JC, Kim E, Nagase H, Casey PJ, Balmain A, Young SG. Absence of the CAAX endoprotease Rce1: effects on cell growth and transformation. Mol Cell Biol. 2002 Jan;22(1):171–181.

Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

January 2002

Volume

22

Issue

1

Start / End Page

171 / 181

Location

United States

Related Subject Headings

  • ras Proteins
  • Tumor Cells, Cultured
  • Transfection
  • Skin Neoplasms
  • Protein Processing, Post-Translational
  • Microscopy, Confocal
  • Mice, Nude
  • Mice
  • Humans
  • Genes, ras