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Chemically synthesized human survivin does not inhibit caspase‐3
Author(s) -
Li Changqing,
Wu Zhibin,
Liu Min,
Pazgier Marzena,
Lu Wuyuan
Publication year - 2008
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.036145.108
Subject(s) - survivin , xiap , inhibitor of apoptosis , caspase , effector , apoptosis , cancer research , chemistry , caspase 7 , caspase 9 , programmed cell death , biology , microbiology and biotechnology , biochemistry
Survivin is a member of the inhibitor of apoptosis protein (IAP) family that blocks cell death by inhibiting the caspase activation pathways. Overexpressed in all common human neoplasms but undetectable in most normal adult tissues, survivin confers tumor resistance to apoptosis and represents an ideal molecular target for therapeutic intervention. How survivin blocks apoptosis, however, has been a subject of intense debate, as evidenced by conflicting reports regarding whether or not survivin can directly bind and inactivate effector caspases. We chemically synthesized large amounts of highly pure human survivin of 142 amino acid residues using native chemical ligation and functionally compared synthetic survivin and a recombinant XIAP—the most intensively studied member of the IAP family. Inhibition assays showed that, while caspase‐3 could be effectively inhibited by XIAP, survivin had no detectable inhibitory activity against the enzyme, even at concentrations several thousand‐fold higher than XIAP. Our finding supports the premise that survivin does not directly inhibit effector caspases.