Inactivation of farnesyltransferase and geranylgeranyltransferase I by caspase-3: Cleavage of the common alpha subunit during apoptosis

Citation
Kw. Kim et al., Inactivation of farnesyltransferase and geranylgeranyltransferase I by caspase-3: Cleavage of the common alpha subunit during apoptosis, ONCOGENE, 20(3), 2001, pp. 358-366
Citations number
49
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
ONCOGENE
ISSN journal
0950-9232 → ACNP
Volume
20
Issue
3
Year of publication
2001
Pages
358 - 366
Database
ISI
SICI code
0950-9232(20010118)20:3<358:IOFAGI>2.0.ZU;2-G
Abstract
Caspase plays an important role in apoptosis. We report here that farnesylt ransferase(geranylgeranyltransferase (FTase/GGTase)-alpha, a common subunit of FTase (alpha/beta (FTase)) and GGTase I (alpha/beta (GGTase)), was clea ved by caspase-3 during apoptosis, FTase/GGTase-alpha (49 kDa) was cleaved to 35 kDa (p35) in the Rat-2/H-ras, W4 and Rat-1 cells treated with FTase i nhibitor (LB42708), anti-Fas antibody and etoposide, respectively. This cle avage was inhibited by caspase-inhibitors (YVAD-cmk, DEVID-cho), Serial N-t erminal deletions and site-directed mutagenesis showed that Asp59 of FTase/ GGTase-alpha was cleaved by caspase-3. The common FTase/GGTase-alpha subuni t, but not the beta subunits, of the FTase or GGTase I protein complexes pu rified from baculovirus-infected SF-9 cells was cleaved to be inactivated b y purified caspase-3. In contrast, FTase mutant protein complex [(D(59)A)al pha/beta (FTase)] was resistant to caspase-3. Expression of either the clea vage product (60-379) or anti-sense of FTase/GGTase-alpha induced cell deat h in Rat-2/H-ras cells. Furthermore, expression of (D(59)A)FTase/GCTase-alp ha mutant significantly desensitized cells to etoposide-induced death. Take n together, we suggest that cleavage of prenyltransferase by caspase contri butes to the progression of apoptosis.