title: Domain analysis of Ras-association domain family member 6 upon interaction with MDM2.
abstract: The tumor suppressor Ras-association domain family member 6 (RASSF6) has Ras-association domain (RA) and Salvador/RASSF/Hippo domain (SARAH). RASSF6 antagonizes MDM2, stabilizes p53, and induces apoptosis and cell cycle arrest. We previously demonstrated the interaction between RASSF6 and MDM2, but did not determine how both proteins interact with each other. We have shown here that N-terminal, RA, and SARAH domains of RASSF6 interact with MDM2 at distinct regions. RA binds to the RING-finger region of MDM2 and stabilizes p53. SARAH binds RA and blocks the interaction between RA and MDM2. RA overexpression induces p53-dependent apoptosis and senescence. In the presence of active KRas, the interaction between RA and MDM2 is recovered. In this way, RA and SARAH play an important role in Ras-mediated regulation of p53.
authors.affiliation: Department of Medical Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Japan.
authors.forename: Aradhan
authors.initials: A
authors.lastname: Sarkar
authors.affiliation: Department of Medical Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Iwasa
authors.affiliation: Department of Medical Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Japan.|Department of Biochemistry and Molecular Biology, University of Rajshahi, Bangladesh.
authors.forename: Shakhawoat
authors.initials: S
authors.lastname: Hossain
authors.affiliation: Department of Medical Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Japan.|Department of Breast Oncology Surgery, The Second Affiliated Hospital of Wenzhou Medical University, China.
authors.forename: Xiaoyin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Medical Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Japan.
authors.forename: Takeru
authors.initials: T
authors.lastname: Sawada
authors.affiliation: Department of Medical Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Japan.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Medical Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Maruyama
authors.affiliation: Department of Medical Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Arimoto-Matsuzaki
authors.affiliation: Department of Medical Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Japan.|Center for Brain Integration Research, Tokyo Medical and Dental University, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hata
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D016922:Cellular Senescence / Q000528:radiation effects; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding / Q000528:radiation effects; D000072417:Protein Domains; D055550:Protein Stability / Q000528:radiation effects; D051736:Proto-Oncogene Proteins c-mdm2 / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000528:radiation effects; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2; D020169:Caspases; D020559:Monomeric GTP-Binding Proteins
keywords: MDM2; RASSF6; p53