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KRAS 诱导的肌动蛋白相互作用蛋白:肥胖症、糖尿病和癌症的有效靶点。

KRAS-induced actin-interacting protein: a potent target for obesity, diabetes and cancer.

机构信息

Department of Cell Biology, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.

出版信息

Anticancer Res. 2011 Jul;31(7):2413-7.

Abstract

KRAS-induced actin-interacting protein (KRAP) was originally identified as one of the genes deregulated in colorectal cancer. KRAP encodes a cytoplasmic protein associated with filamentous-actin (F-actin), and the amino acid sequences are highly conserved among KRAP orthologues from fish to mammalian species. We demonstrated that KRAP-deficient mice show altered whole-body energy metabolism and resistance to diet-induced obesity and diabetes. Although the precise mechanisms underlying the metabolic phenotypes in the KRAP-deficient mice remain unclear, KRAP is considered to be a target for metabolism-related diseases. Furthermore, several groups have reported that KRAP is a cancer-associated gene. Further studies on the molecular functions of KRAP in physiological tissues could provide a better understanding of various diseases, and opportunities for intervention in various human diseases. In this review, we summarize the current understanding of KRAP and the roles that it plays in a variety of diseases.

摘要

KRAS 诱导的肌动蛋白相互作用蛋白 (KRAP) 最初被鉴定为结直肠癌中失调的基因之一。KRAP 编码一种与丝状肌动蛋白 (F-actin) 相关的细胞质蛋白,其氨基酸序列在从鱼类到哺乳动物物种的 KRAP 同源物中高度保守。我们证明,缺乏 KRAP 的小鼠表现出全身能量代谢改变,并且对饮食诱导的肥胖和糖尿病具有抗性。尽管 KRAP 缺陷小鼠代谢表型的具体机制尚不清楚,但 KRAP 被认为是与代谢相关疾病的靶点。此外,有几个研究小组报道 KRAP 是一种与癌症相关的基因。进一步研究 KRAP 在生理组织中的分子功能可以更好地理解各种疾病,并为各种人类疾病的干预提供机会。在这篇综述中,我们总结了目前对 KRAP 的认识,以及它在各种疾病中所扮演的角色。

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