Consequences of mevalonate depletion. Differential transcriptional, translational, and post-translational up-regulation of Ras, Rap1a, RhoA, and RhoB

Sarah A. Holstein, Christine L. Wohlford-Lenane, Raymond J. Hohl

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Ras-related proteins are small GTPases that are post-translationally modified with mevalonate-derived isoprenoids. Although the effects of inhibition of isoprenylation on protein function have been examined, the consequences of depletion of isoprenoid pools on regulation of expression of isoprenylated proteins have yet to be investigated. In these studies we have shown that depletion of mevalonate results in increased total levels of Ras, Rap1a, RhoA, and RhoB in K562 cells. Cycloheximide and [35S]methionine pulse/pulse-chase experiments reveal that mevalonate depletion increases the de novo synthesis of Ras and RhoA and decreases the degradation of existing Ras and RhoA protein. Pretreatment with actinomycin D completely prevents the induced up-regulation of RhoB and only partially prevents the up-regulation of Ras, Rap1a, and RhoA. Although depletion of mevalonate does not alter steady state levels of Ras mRNA, there is an increase in RhoB mRNA. Our results are the first to demonstrate that mevalonate depletion induces up-regulation of Ras and Ras-related proteins by discrete mechanisms that include modulation of transcriptional, translational, and post-translational processes.

Original languageEnglish (US)
Pages (from-to)10678-10682
Number of pages5
JournalJournal of Biological Chemistry
Volume277
Issue number12
DOIs
StatePublished - Mar 22 2002

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Mevalonic Acid
Up-Regulation
ras Proteins
Terpenes
Proteins
rhoA GTP-Binding Protein
Protein Prenylation
Messenger RNA
Monomeric GTP-Binding Proteins
K562 Cells
Dactinomycin
Cycloheximide
Methionine
Modulation
Degradation
Experiments

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Consequences of mevalonate depletion. Differential transcriptional, translational, and post-translational up-regulation of Ras, Rap1a, RhoA, and RhoB. / Holstein, Sarah A.; Wohlford-Lenane, Christine L.; Hohl, Raymond J.

In: Journal of Biological Chemistry, Vol. 277, No. 12, 22.03.2002, p. 10678-10682.

Research output: Contribution to journalArticle

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