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RASSF6; the Putative Tumor Suppressor of the RASSF Family

Department of Medical Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
Center for Brain Integration Research, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
Author to whom correspondence should be addressed.
Academic Editor: Reinhard Dammann
Cancers 2015, 7(4), 2415-2426;
Received: 2 November 2015 / Revised: 1 December 2015 / Accepted: 1 December 2015 / Published: 9 December 2015
(This article belongs to the Special Issue RASSF Signalling in Cancer)
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Humans have 10 genes that belong to the Ras association (RA) domain family (RASSF). Among them, RASSF7 to RASSF10 have the RA domain in the N-terminal region and are called the N-RASSF proteins. In contradistinction to them, RASSF1 to RASSF6 are referred to as the C-RASSF proteins. The C-RASSF proteins have the RA domain in the middle region and the Salvador/RASSF/Hippo domain in the C-terminal region. RASSF6 additionally harbors the PSD-95/Discs large/ZO-1 (PDZ)-binding motif. Expression of RASSF6 is epigenetically suppressed in human cancers and is generally regarded as a tumor suppressor. RASSF6 induces caspase-dependent and -independent apoptosis. RASSF6 interacts with mammalian Ste20-like kinases (homologs of Drosophila Hippo) and cross-talks with the Hippo pathway. RASSF6 binds MDM2 and regulates p53 expression. The interactions with Ras and Modulator of apoptosis 1 (MOAP1) are also suggested by heterologous protein-protein interaction experiments. RASSF6 regulates apoptosis and cell cycle through these protein-protein interactions, and is implicated in the NF-κB and JNK signaling pathways. We summarize our current knowledge about RASSF6 and discuss what common and different properties RASSF6 and the other C-RASSF proteins have. View Full-Text
Keywords: apoptosis; cell cycle; Hippo pathway; MDM2; p53; Ras; tumor suppressor apoptosis; cell cycle; Hippo pathway; MDM2; p53; Ras; tumor suppressor

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Iwasa, H.; Jiang, X.; Hata, Y. RASSF6; the Putative Tumor Suppressor of the RASSF Family. Cancers 2015, 7, 2415-2426.

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