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STAM 结合蛋白通过稳定 SLUG 来调节黑色素瘤转移。

STAM-binding protein regulates melanoma metastasis through SLUG stabilization.

机构信息

Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.

Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.

出版信息

Biochem Biophys Res Commun. 2018 Dec 9;507(1-4):484-488. doi: 10.1016/j.bbrc.2018.11.068. Epub 2018 Nov 16.

Abstract

STAM-binding protein, STAMBP, is a JAMM-family deubiquitinating enzyme containing the microtubule-interacting/transport domain and STAM-binding domain. Although the biological importance of STAMBP in development has been recognized because the microcephaly-capillary malformation syndrome in human is caused by its somatic mutations, the role of STAMBP in cancer has not yet been determined. In this study, we demonstrate that STAMBP is a key molecule for regulating melanoma migration and invasion, but not survival, by knocking down STAMBP in vitro. STAMBP regulates SLUG expression through a post-transcriptional mechanism to control protein stability and further contributes to the in vivo metastatic potential of melanoma. Collectively, these results indicate the importance of STAMBP in melanoma metastasis by regulating SLUG. It is therefore a potential therapeutic target.

摘要

支架相关膜蛋白(STAM)结合蛋白(STAMBP)是一种含有微管相互作用/运输结构域和 STAM 结合结构域的 JAMM 家族去泛素化酶。虽然 STAMBP 在人类微脑-毛细血管畸形综合征中的体细胞突变导致的发育中的生物学重要性已被认识,但 STAMBP 在癌症中的作用尚未确定。在这项研究中,我们通过体外敲低 STAMBP 证明 STAMBP 是调节黑色素瘤迁移和侵袭的关键分子,但对生存没有影响。STAMBP 通过转录后机制调节 SLUG 的表达,控制蛋白质稳定性,并进一步促进黑色素瘤的体内转移潜能。总的来说,这些结果表明 STAMBP 通过调节 SLUG 在黑色素瘤转移中的重要性。因此,它是一个潜在的治疗靶点。

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