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

Reiss K; Yumet G; Shan SHuang ZAlnemri ESrinivasula SMWang JYMorrione ABaserga R

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

机译：合成的糖肽序列胰岛素样生长因子受体诱导细胞凋亡和抑制肿瘤的生长。

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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. Copyright 1999 Wiley-Liss, Inc.

机译：虽然1型胰岛素样生长因子受体(IGF-IR)是一种强有力的抑制剂细胞凋亡,其糖基序列发送相互矛盾的信号,包括一个清楚proapoptotic信号。肽,肽的序列1298年IGF-IR从1282年残渣残留(糖基的β亚基)。吸收到细胞内,我们与硬脂酸NH-terminus一半。的细胞,抑制DNA合成和导致细胞凋亡,而炒肽(没有硬脂酸硬脂酸)和肽2是完全无效的。细胞在anchorage-independent时有效条件比当他们在单层生长文化。抑制人类前列腺细胞系的生长在裸小鼠。2是由bcl - 2的表达或抑制主导-半胱天冬酶的突变体9。其他数据表明,肽2似乎并不直接与IGF-IR竞争常见的基质,但其proapoptotic作用与激活的能力半胱天冬酶级联。

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《Journal of Cellular Physiology》 |1999年第1期|124-135|共12页
作者
Reiss K; Yumet G; Shan SHuang ZAlnemri ESrinivasula SMWang JYMorrione ABaserga R;
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作者单位

Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.;

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原文格式 PDF
正文语种英语
中图分类细胞生物学;
关键词
C-Terminus; Insulin-Like Growth Factor Receptor; Insulin-Like-Growth Factor I ReceptorCaspasespeptide fragmentPeptidesApoptosistumor growthstearic acid;

机译：糖基;胰岛素样生长因子受体,胰岛素样生长因子IReceptorCaspasespeptidefragmentPeptidesApoptosistumor growthstearic酸;

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

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