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

Oncogene
K W KimY K Jung

Abstract

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 prenyltrans...Continue Reading

References

Oct 1, 1989·Current Opinion in Immunology·N NakayamaT Yokota
Jan 1, 1996·Annual Review of Biochemistry·F L Zhang, P J Casey
Oct 18, 1996·Cell·E S AlnemriJ Yuan
Mar 14, 1997·The Journal of Biological Chemistry·N MargolinD J Livingston
Jun 23, 1998·The Journal of Biological Chemistry·E W HumkeV M Dixit
Aug 28, 1998·Science·N A Thornberry, Y Lazebnik
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·N SuzukiF Tamanoi
Jan 23, 1999·Oncogene·G NuñezN Inohara
Feb 13, 1999·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·L A O'Reilly, A Strasser
Mar 17, 1999·Biochimica Et Biophysica Acta·W G Tatton, C W Olanow
Mar 30, 1999·Experimental Cell Research·B ZhivotovskyS Orrenius
Aug 18, 1999·Proceedings of the National Academy of Sciences of the United States of America·K GeG C Prendergast
Oct 16, 1999·The Journal of Biological Chemistry·M P ScheidV Duronio
Dec 1, 1999·Cell Death and Differentiation·D W Nicholson

❮ Previous
Next ❯

Citations

Oct 12, 2012·Apoptosis : an International Journal on Programmed Cell Death·Daleep K AroraAnjaneyulu Kowluru
Oct 25, 2011·Nature Reviews. Cancer·Norbert BerndtSaïd M Sebti
Oct 15, 2010·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Wasanthi SubasingheAnjaneyulu Kowluru
Sep 8, 2017·Diabetes, Obesity & Metabolism·Anjaneyulu Kowluru
Mar 26, 2003·Cell Death and Differentiation·U FischerK Schulze-Osthoff
Dec 21, 2006·Protoplasma·F GroligP Galland

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis