Stable Identifier
Reaction [binding]
Homo sapiens
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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).

Literature References
PubMed ID Title Journal Year
18332145 IMP modulates KSR1-dependent multivalent complex formation to specify ERK1/2 pathway activation and response thresholds

Chen, C, Lewis, RE, White, MA

J. Biol. Chem. 2008
14724641 Ras regulates assembly of mitogenic signalling complexes through the effector protein IMP

Matheny, SA, Chen, C, Kortum, RL, Razidlo, GL, Lewis, RE, White, MA

Nature 2004
19091743 Signaling threshold regulation by the Ras effector IMP

Matheny, SA, White, MA

J. Biol. Chem. 2009
23105109 Direct and indirect control of mitogen-activated protein kinase pathway-associated components, BRAP/IMP E3 ubiquitin ligase and CRAF/RAF1 kinase, by the deubiquitylating enzyme USP15

Hayes, SD, Liu, H, MacDonald, E, Sanderson, CM, Coulson, JM, Clague, MJ, Urbé, S

J. Biol. Chem. 2012
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