Premium
Synthetic peptide sequence from the C‐terminus of the insulin‐like growth factor‐I receptor that induces apoptosis and inhibition of tumor growth
Author(s) -
Reiss Krzysztof,
Yumet Gladys,
Shan Simei,
Huang Ziwei,
Alnemri Emad,
Srinivasula Srinivasa M.,
Wang Jin Ying,
Morrione Andrea,
Baserga Renato
Publication year - 1999
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199910)181:1<124::aid-jcp13>3.0.co;2-0
Subject(s) - peptide , apoptosis , peptide sequence , receptor , cell culture , epidermal growth factor , biology , signal peptide , c terminus , chemistry , microbiology and biotechnology , biochemistry , amino acid , genetics , gene
Although the type 1 insulin‐like growth factor receptor (IGF‐IR) is a potent inhibitor of apoptosis, its C‐terminus sequence sends contradictory signals, including a clearly proapoptotic signal. We have synthesized a peptide, peptide 2, having the sequence of the IGF‐IR from residue 1282 to residue 1298 (C‐terminus of the β subunit). To favor its uptake into cells, we linked it to a stearic acid moiety at its NH‐terminus. Peptide 2 is taken up by the cells, where it inhibits DNA synthesis and causes apoptosis, while a scrambled peptide (with stearic acid) and peptide 2 without stearic acid are completely ineffective. Peptide 2 is more effective when cells are in anchorage‐independent conditions than when they grow in monolayer cultures. Accordingly, we find that peptide 2 can inhibit the growth of a human prostatic cell line in nude mice. The proapoptotic effect of peptide 2 is inhibited by the expression of Bcl‐2 or by a dominant negative mutant of caspase 9. These and other data indicate that peptide 2 does not seem to be competing directly with the IGF‐IR for common substrates, but that its proapoptotic effect is related to its ability to activate the caspase cascade. J. Cell. Physiol. 181:124–135, 1999. © 1999 Wiley‐Liss, Inc.