RASSF5：在体内是一种MST激活剂和肿瘤抑制因子，但在体外情况相反。
RASSF5: An MST activator and tumor suppressor in vivo but opposite in vitro.
作者信息
Liao Tsung-Jen, Tsai Chung-Jung, Jang Hyunbum, Fushman David, Nussinov Ruth
机构信息
Cancer and Inflammation Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA; Biophysics Program, University of Maryland, College Park, MD 20742, USA.
Cancer and Inflammation Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
出版信息
Curr Opin Struct Biol. 2016 Dec;41:217-224. doi: 10.1016/j.sbi.2016.09.001. Epub 2016 Sep 17.
Is RASSF5 a tumor suppressor or activator? RASSF5 links K-Ras and the Hippo pathway. Hippo's signaling promotes YAP1 phosphorylation and degradation. YAP1 overexpression promotes cancer. Most reports point to RASSF5 suppressing cancer; however, some point to its promoting cancer. Our mechanistic view explains how RASSF5 can activate MST1/2 and suppress cancer in vivo; but inhibits MST1/2 in vitro. We propose that both activation and inhibition of MST1/2 can take place via SARAH heterodimerization. Our thesis in vivo, membrane-anchored Ras dimers (or nanoclusters) can promote SARAH domain heterodimerization, Raf-like MST1/2 kinase domain homodimerization and trans-autophosphorylation. In contrast, in vitro, K-Ras binding also releases the RASSF5 SARAH stimulating MST1/2's SARAH heterodimerization; however, without membrane, no MST1/2 kinase domain homodimerization/trans-autophosphorylation.
RASSF5是肿瘤抑制因子还是激活因子？RASSF5连接K-Ras和Hippo信号通路。Hippo信号通路促进YAP1磷酸化和降解。YAP1过表达促进癌症发生。大多数报道指出RASSF5抑制癌症；然而，也有一些报道指出它促进癌症。我们的机制观点解释了RASSF5如何在体内激活MST1/2并抑制癌症；但在体外抑制MST1/2。我们提出，MST1/2的激活和抑制都可以通过SARAH异源二聚化发生。我们的观点是，在体内，膜锚定的Ras二聚体（或纳米簇）可以促进SARAH结构域异源二聚化、Raf样MST1/2激酶结构域同源二聚化和反式自磷酸化。相比之下，在体外，K-Ras结合也会释放RASSF5的SARAH，刺激MST1/2的SARAH异源二聚化；然而，没有膜的情况下，不会发生MST1/2激酶结构域同源二聚化/反式自磷酸化。
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