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Domain analysis of Ras‐association domain family member 6 upon interaction with MDM 2
Author(s) -
Sarkar Aradhan,
Iwasa Hiroaki,
Hossain Shakhawoat,
Xu Xiaoyin,
Sawada Takeru,
Shimizu Takanobu,
Maruyama Junichi,
ArimotoMatsuzaki Kyoko,
Hata Yutaka
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12551
Subject(s) - mdm2 , suppressor , domain (mathematical analysis) , chemistry , apoptosis , microbiology and biotechnology , protein–protein interaction , biology , cancer research , biochemistry , gene , mathematical analysis , mathematics
The tumor suppressor Ras‐association domain family member 6 ( RASSF 6) has Ras‐association domain ( RA ) and Salvador/ RASSF /Hippo domain ( SARAH ). RASSF 6 antagonizes MDM 2, stabilizes p53, and induces apoptosis and cell cycle arrest. We previously demonstrated the interaction between RASSF 6 and MDM 2, but did not determine how both proteins interact with each other. We have shown here that N‐terminal, RA , and SARAH domains of RASSF 6 interact with MDM 2 at distinct regions. RA binds to the RING ‐finger region of MDM 2 and stabilizes p53. SARAH binds RA and blocks the interaction between RA and MDM 2. RA overexpression induces p53‐dependent apoptosis and senescence. In the presence of active KR as, the interaction between RA and MDM 2 is recovered. In this way, RA and SARAH play an important role in Ras‐mediated regulation of p53.