RASSF5: An MST activator and tumor suppressor in vivo but opposite in vitro

Tsung Jen Liao, Chung Jung Tsai, Hyunbum Jang, David Fushman, Ruth Nussinov

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish
Pages (from-to)217-224
Number of pages8
JournalCurrent Opinion in Structural Biology
StatePublished - 1 Dec 2016


FundersFunder number
National Institutes of HealthHHSN261200800001E, GM065334
National Cancer InstituteZIABC010441
Frederick National Laboratory for Cancer Research


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