BRAP is a negative regulator of the RAF/MAPK cascade that inhibits the homo- and heterodimerization of KSR1 and RAF and preventing downstream signal propagation (Matheny et al, 2004; Chen et al, 2008; reviewed in Matheny et al, 2009). Upon RAS stimulation, BRAP binds to RAS:GTP. This stimulates BRAP's E3 HECT ubiquitin ligase activity, promoting its autoubiquitination and thereby relieving the inhibition of KSR1 activity (Matheny et al, 2004; reviewed in Matheny et al, 2009). USP15 is a deubiquitinase that stabilizes BRAP protein levels and thus acts to dampen MAPK signaling (Hayes et al, 2013).
White, MA, Kortum, RL, Lewis, RE, Razidlo, GL, Matheny, SA, Chen, C
White, MA, Lewis, RE, Chen, C
White, MA, Matheny, SA
Clague, MJ, Coulson, JM, MacDonald, E, Sanderson, CM, Urbé, S, Liu, H, Hayes, SD
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