ICE-LAP6, a novel member of the ICE/Ced-3 gene family, is activated by the cytotoxic T cell protease granzyme B

Hangjun Duan, Kim Orth, Arul M. Chinnaiyan, Guy G. Poirier, Christopher J. Froelich, Wei Wu He, Vishva M. Dixit

Research output: Contribution to journalArticle

295 Citations (Scopus)

Abstract

Members of the ICE/Ced-3 gene family are likely effector components of the cell death machinery. Here, we characterize a novel member of this family designated ICE-LAP6. By phylogenetic analysis, ICE-LAP6 is classified into the Ced-3 subfamily which includes Ced-3, Yama/CPP32/apopain, Mch2, and ICE- LAP3/Mch3/CMH-1. Interestingly, ICE-LAP6 contains an active site QACGG pentapeptide, rather than the QACRG pentapeptide shared by other family members. Overexpression of ICE-LAP6 induces apoptosis in MCF7 breast carcinoma cells. More importantly, ICE-LAP6 is proteolytically processed into an active cysteine protease by granzyme B, an important component of cytotoxic T cell-mediated apoptosis. Once activated, ICE-LAP6 is able to cleave the death substrate poly(ADP-ribose) polymerase into signature apoptotic fragments.

Original languageEnglish (US)
Pages (from-to)16720-16724
Number of pages5
JournalJournal of Biological Chemistry
Volume271
Issue number28
DOIs
StatePublished - 1996

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Granzymes
T-cells
Peptide Hydrolases
Genes
Apoptosis
T-Lymphocytes
Cysteine Proteases
Poly(ADP-ribose) Polymerases
Cell death
Caspase 3
Machinery
Catalytic Domain
Cell Death
Cells
Breast Neoplasms
Substrates

ASJC Scopus subject areas

  • Biochemistry

Cite this

ICE-LAP6, a novel member of the ICE/Ced-3 gene family, is activated by the cytotoxic T cell protease granzyme B. / Duan, Hangjun; Orth, Kim; Chinnaiyan, Arul M.; Poirier, Guy G.; Froelich, Christopher J.; He, Wei Wu; Dixit, Vishva M.

In: Journal of Biological Chemistry, Vol. 271, No. 28, 1996, p. 16720-16724.

Research output: Contribution to journalArticle

Duan, Hangjun ; Orth, Kim ; Chinnaiyan, Arul M. ; Poirier, Guy G. ; Froelich, Christopher J. ; He, Wei Wu ; Dixit, Vishva M. / ICE-LAP6, a novel member of the ICE/Ced-3 gene family, is activated by the cytotoxic T cell protease granzyme B. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 28. pp. 16720-16724.
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AU - Poirier, Guy G.

AU - Froelich, Christopher J.

AU - He, Wei Wu

AU - Dixit, Vishva M.

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