Inactivation of farnesyltransferase and geranylgeranyltransferase I by caspase-3: cleavage of the common alpha subunit during apoptosis.
In: Oncogene, Jg. 20 (2001-01-18), Heft 3, S. 358-66
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Zugriff:
Caspase plays an important role in apoptosis. We report here that farnesyltransferase/geranylgeranyltransferase (FTase/GGTase)-alpha, a common subunit of FTase (alpha/beta(FTase)) and GGTase I (alpha/beta(GGTase)), was cleaved 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 inhibitor (LB42708), anti-Fas antibody and etoposide, respectively. This cleavage was inhibited by caspase-inhibitors (YVAD-cmk, DEVD-cho). Serial N-terminal deletions and site-directed mutagenesis showed that Asp59 of FTase/GGTase-alpha was cleaved by caspase-3. The common FTase/GGTase-alpha subunit, but not the beta subunits, of the FTase or GGTase I protein complexes purified from baculovirus-infected SF-9 cells was cleaved to be inactivated by purified caspase-3. In contrast, FTase mutant protein complex [(D(59)A)alpha/beta(FTase)] was resistant to caspase-3. Expression of either the cleavage product (60-379) or anti-sense of FTase/GGTase-alpha induced cell death in Rat-2/H-ras cells. Furthermore, expression of (D(59)A)FTase/GGTase-alpha mutant significantly desensitized cells to etoposide-induced death. Taken together, we suggest that cleavage of prenyltransferase by caspase contributes to the progression of apoptosis.
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Inactivation of farnesyltransferase and geranylgeranyltransferase I by caspase-3: cleavage of the common alpha subunit during apoptosis.
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Autor/in / Beteiligte Person: | Kim, KW ; Chung, HH ; Chung, CW ; Kim, IK ; Miura, M ; Wang, S ; Zhu, H ; Moon, KD ; Rha, GB ; Park, JH ; Jo, DG ; Woo, HN ; Song, YH ; Kim, BJ ; Yuan, J ; Jung, YK |
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Zeitschrift: | Oncogene, Jg. 20 (2001-01-18), Heft 3, S. 358-66 |
Veröffentlichung: | <2002->: Basingstoke : Nature Publishing Group ; <i>Original Publication</i>: Basingstoke, Hampshire, UK : Scientific & Medical Division, MacMillan Press, c1987-, 2001 |
Medientyp: | academicJournal |
ISSN: | 0950-9232 (print) |
DOI: | 10.1038/sj.onc.1204099 |
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