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

Ki Woo Kim, Hyun Ho Chung, Chul Woong Chung, In Ki Kim, Masayuki Miura, Suyue Wang, Hong Zhu, Kyung Duk Moon, Geun Bae Rha, Jy Hyun Park, Dong Gyu Jo, Ha Na Woo, Yu Hyun Song, Byung Ju Kim, Junying Yuan, Yong Keun Jung

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15 Citations (Scopus)


Caspase plays an important role in apoptosis. We report here that farnesyltransferase/geranylgeranyltransferase (FTase/GGTase)-α, a common subunit of FTase (α/ βFTase) and GGTase I (α/βGGTase), was cleaved by caspase-3 during apoptosis. FTase/GGTase-α (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-α was cleaved by caspase-3. The common FTase/GGTase-α subunit, but not the β 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 [(D59A)α/βFTase] was resistant to caspase-3. Expression of either the cleavage product (60-379) or anti-sense of FTase/GGTase-α induced cell death in Rat- 2/H-ras cells. Furthermore, expression of (D59A)FTase/ GGTase-α mutant significantly desensitized cells to etoposide-induced death. Taken together, we suggest that cleavage of prenyltransferase by caspase contributes to the progression of apoptosis.

Original languageEnglish
Pages (from-to)358-366
Number of pages9
Issue number3
Publication statusPublished - 2001 Jan 18

Bibliographical note

Funding Information:
We thank S Nagata and J Goldstein for W4 cells and hamster caspase-3 antibody, respectively. We thank N Spoerel for critical reading of this manuscript. This work was supported by Brain Korea 21 project and in part by grants from the KOSEF (97-0401-07-01-5) and Molecular Medicine Research.

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research


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