PMID:23118896

Citation	Atabakhsh, E and Schild-Poulter, C (2012) RanBPM Is an Inhibitor of ERK Signaling. PLoS ONE 7:e47803
Abstract	Ran-binding protein M (RanBPM) is a nucleocytoplasmic protein of yet unknown function. We have previously shown that RanBPM inhibits expression of the anti-apoptotic factor Bcl-2 and promotes apoptosis induced by DNA damage. Here we show that the effects of RanBPM on Bcl-2 expression occur through a regulation of the ERK signaling pathway. Transient and stable down-regulation of RanBPM stimulated ERK phosphorylation, leading to Bcl-2 up-regulation, while re-expression of RanBPM reversed these effects. RanBPM was found to inhibit MEK and ERK activation induced by ectopic expression of active RasV12. Activation of ERK by active c-Raf was also prevented by RanBPM. Expression of RanBPM correlated with a marked decrease in the protein levels of ectopically expressed active c-Raf and also affected the expression of endogenous c-Raf. RanBPM formed a complex with both active c-Raf, consisting of the C-terminal kinase domain, and endogenous c-Raf in mammalian cells. In addition, RanBPM was found to decrease the binding of Hsp90 to c-Raf. Finally, we show that loss of RanBPM expression confers increased cell proliferation and cell migration properties to HEK293 cells. Altogether, these findings establish RanBPM as a novel inhibitor of the ERK pathway through an interaction with the c-Raf complex and a regulation of c-Raf stability, and provide evidence that RanBPM loss of expression results in constitutive activation of the ERK pathway and promotes cellular events leading to cellular transformation and tumorigenesis.
Links	PubMed PMC3485245 Online version:10.1371/journal.pone.0047803
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:RANB9		GO:0070373: negative regulation of ERK1 and ERK2 cascade	ECO:0000315:		P		Figure 2 shows RanBPM is a negative regulator of ERK1/2 activation through use of western blots and antibody precitpitation via enhanced phosphorylation	complete CACAO 5672
HUMAN:RANB9	involved_in	GO:0070373: negative regulation of ERK1 and ERK2 cascade	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

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