Reactome | XPO1 binds p-S69,73 MITF-M

XPO1 binds p-S69,73 MITF-M

Stable Identifier

R-HSA-9824979

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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GSK3B-dependent phosphorylation of MITF-M at residue S69 promotes its interaction with the nuclear export factor XPO1, also known as CRM1 (Ngeow et al, 2018). Nuclear export of MITF-M is dependent on the nuclear export sequence MxMLxM located at residues 74-80. Mutation of this site abrogates nuclear export of an MITF-M reporter in response to MAPK activation by TPA (12-O-tetradecanoylphorbol-13 acetate), supporting a model where sequential phosphorylations by MAPK1 and GSK3B at MITF-M serine residues S73 and S69 promote XPO1-dependent relocation of MITF-M to the cytosol (Ngeow et al, 2018; reviewed in Goding and Arnheiter, 2019). MITF-M has also been shown to interact with other nuclear pore export factors including KPNA1, KPNB1, KPNA4, NUP50, NUP153, NPM1, NOP14, TNPO1 and XPO5, reflecting regulation of MITF localization and/or a tethering of MITF transcription factor activity with RNA export (Laurette et al, 2015).

Literature References

PubMed ID	Title	Journal	Year
25803486	Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cells Laurette, P, Strub, T, Koludrovic, D, Keime, C, Le Gras, S, Seberg, H, Van Otterloo, E, Imrichova, H, Siddaway, R, Aerts, S, Cornell, RA, Mengus, G, Davidson, I	Elife	2015
31123060	MITF-the first 25 years Goding, CR, Arnheiter, H	Genes Dev	2019
30150413	BRAF/MAPK and GSK3 signaling converges to control MITF nuclear export Ngeow, KC, Friedrichsen, HJ, Li, L, Zeng, Z, Andrews, S, Volpon, L, Brunsdon, H, Berridge, G, Picaud, S, Fischer, R, Lisle, R, Knapp, S, Filippakopoulos, P, Knowles, H, Steingrímsson, E, Borden, KLB, Patton, EE, Goding, CR	Proc Natl Acad Sci U S A	2018