Synthetic peptide sequence from the C-terminus of the insulin-like growth factor-I receptor that induces apoptosis and inhibition of tumor growth
| Autor: | Emad S. Alnemri, Srinivasa M. Srinivasula, Ziwei Huang, Andrea Morrione, Simei Shan, Jin Ying Wang, Renato Baserga, Gladys Yumet, Krzysztof Reiss |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Physiology
Clinical Biochemistry Molecular Sequence Data Mice Nude Peptide Apoptosis Inhibitor of apoptosis Receptor IGF Type 1 Mice Growth factor receptor Tumor Cells Cultured Animals Humans Amino Acid Sequence Peptide sequence Caspase chemistry.chemical_classification Caspase-9 biology Cell Death C-terminus Cell Biology DNA Fibroblasts Molecular biology Peptide Fragments Enzyme Activation chemistry Cell culture Caspases biology.protein Cell Division Neoplasm Transplantation |
| Zdroj: | Journal of cellular physiology. 181(1) |
| ISSN: | 0021-9541 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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