The phosphorylation of PHF5A by TrkA-ERK1/2-ABL1 cascade regulates centrosome separation.
Cell Death Dis
; 14(2): 98, 2023 02 09.
Article
en En
| MEDLINE
| ID: mdl-36759599
ABSTRACT
During interphase, the newly duplicated pairs of centrosomes are held together by a centrosome linker, and the centrosome separation needs the disruption of this linker to induce the duplicated centrosomes separating into two distinct microtubule organization centers. The mechanism of regulating centrosome separation is however poorly understood. Here, we demonstrated that the phosphorylation of PHF5A at Y36 by the TrkA-ERK1/2-ABL1 cascade plays a critical role in regulating centrosome separation. PHF5A, a well-characterized spliceosome component, is enriched in the centrosome. The pY36-PHF5A promotes the interaction between CEP250 and Nek2A in a spliceosomal-independent manner, which leads to premature centrosome separation. Furthermore, the unmatured centrosome remodels the microtubule and subsequently regulates cell proliferation and migration. Importantly, we found that the phosphorylation cascade of TrkA-ERK1/2-ABL1-PHF5A is hyper-regulated in medulloblastoma. The inhibition of this cascade can induce senescence and restrict the proliferation of medulloblastoma. Our findings on this phosphorylation cascade in regulating centrosome separation could provide a series of potential targets for restricting the progress of medulloblastoma.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Cerebelosas
/
Meduloblastoma
Límite:
Humans
Idioma:
En
Revista:
Cell Death Dis
Año:
2023
Tipo del documento:
Article
País de afiliación:
China