Phosphorylation of serine 323 of ASB2α is pivotal for the targeting of filamin A to degradation.
Cell Signal
; 25(12): 2823-30, 2013 Dec.
Article
en En
| MEDLINE
| ID: mdl-24044920
ABSTRACT
ASB proteins are the specificity subunits of cullin5-RING E3 ubiquitin ligases (CRL5) that play roles in ubiquitin-mediated protein degradation. However, how their activity is regulated remains poorly understood. Here, we unravel a novel mechanism of regulation of a CRL5 through phosphorylation of its specificity subunit ASB2α. Indeed, using mass spectrometry, we showed for the first time that ASB2α is phosphorylated and that phosphorylation of serine-323 (Ser-323) of ASB2α is crucial for the targeting of the actin-binding protein filamin A (FLNa) to degradation. Mutation of ASB2α Ser-323 to Ala had no effect on intrinsic E3 ubiquitin ligase activity of ASB2α but abolished the ability of ASB2α to induce degradation of FLNa. In contrast, the ASB2α Ser-323 to Asp phosphomimetic mutant induced acute degradation of FLNa. Moreover, inhibition of the extracellular signal-regulated kinases 1 and 2 (Erk1/2) activity reduced ASB2α-mediated FLNa degradation. We further showed that the subcellular localization of ASB2α to actin-rich structures is dependent on ASB2α Ser-323 phosphorylation and propose that the interaction with FLNa depends on the electrostatic potential redistribution induced by the Ser-323 phosphate group. Taken together, these data unravel an important mechanism by which ASB2α-mediated FLNa degradation can be regulated.
Palabras clave
AML; APL; AR; ASB; CID; CRL5; Cullin-RING E3 ubiquitin ligase; E3; E3 ubiquitin ligase; ETD; Erk; FLN; Filamin; Mass spectrometry; Post-translational modifications; acute myeloid leukemia; acute promyelocytic leukemia; ankyrin repeat; collision-induced dissociation; cullin5-RING E3 ubiquitin ligases; electron transfer dissociation; extracellular signal-regulated kinase; filamin
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Serina
/
Proteínas Supresoras de la Señalización de Citocinas
/
Proteolisis
/
Filaminas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Signal
Año:
2013
Tipo del documento:
Article
País de afiliación:
Francia