Using inhibitors of prenylation to block localization and transforming activity.

Using inhibitors of prenylation to block localization and transforming activity. Research Abstract Details 

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Using inhibitors of prenylation to block localization and transforming activity. Abstract Text:

Anastacia C Berzat,Donita C Brady,James J Fiordalisi,Adrienne D Cox,

The proper subcellular localization and biological activity of most Ras and Rho family small GTPases are dependent on their posttranslational modification by isoprenylation. Farnesyltransferase (FTase) and geranylgeranyl transferase I (GGTase I) are the prenyltransferases that catalyze the irreversible attachment of C15 farnesyl (Ras, Rnd) or C20 (R-Ras, Ral, Rap, Rho, Rac, Cdc42) isoprenoid lipid moieties to these small GTPases and other proteins. Therefore, pharmacological inhibitors of FTase (FTIs) and GGTase I (GGTIs) have been developed to prevent these modifications and thereby to block the lipid-mediated association of Ras and Rho proteins with cellular membranes and the consequent signaling and transforming activities. In addition, other small molecule inhibitors such as farnesyl thiosalicylic acid (FTS) can compete with the isoprenoid moiety of small GTPases for membrane binding sites. Finally, endogenous regulatory proteins such as RhoGDIs can bind to and mask the prenyl groups of small GTPases, leading to their sequestration from membranes. We describe here methods to use each of these categories of prenylation inhibitors to manipulate and investigate the subcellular localization patterns and transforming potential of these Ras and Rho family GTPases.

Using inhibitors of prenylation to block localization and transforming activity. Publishing Authors By Initials

AC Berzat,DC Brady,JJ Fiordalisi,AD Cox,

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Using inhibitors of prenylation to block localization and transforming activity. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Methods in enzymology

VOLUME: 407

Page Numbers: 575-97

Journal Abbreviation: Meth. Enzymol.

ISSN: 0076-6879

DAY: 7

MONTH: 06

YEAR: 2005

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LANGUAGE: eng

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Country: United States

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MEDLINETA: Methods Enzymol

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