Synthetic peptide sequence from the C-terminus of the insulin-like growth factor-I receptor that induces apoptosis and inhibition of tumor growth.

Abstract:

: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 beta 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.

journal_name

J Cell Physiol

authors

Reiss K,Yumet G,Shan S,Huang Z,Alnemri E,Srinivasula SM,Wang JY,Morrione A,Baserga R

doi

10.1002/(SICI)1097-4652(199910)181:1<124::AID-JCP1

keywords:

subject

Has Abstract

pub_date

1999-10-01 00:00:00

pages

124-35

issue

1

eissn

0021-9541

issn

1097-4652

pii

10.1002/(SICI)1097-4652(199910)181:1<124::AID-JCP1

journal_volume

181

pub_type

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