ZDHHC12-mediated claudin-3 -palmitoylation determines ovarian cancer progression
Acta Pharmaceutica Sinica B
; (6): 1426-1439, 2020.
Article
в En
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| ID: wpr-828798
Ответственная библиотека:
WPRO
ABSTRACT
The membrane protein claudin-3 (CLDN3) is critical for the formation and maintenance of tight junction and its high expression has been implicated in dictating malignant progression in various cancers. However, the post-translational modification of CLDN3 and its biological function remains poorly understood. Here, we report that CLDN3 is positively correlated with ovarian cancer progression both and Of interest, CLDN3 undergoes -palmitoylation on three juxtamembrane cysteine residues, which contribute to the accurate plasma membrane localization and protein stability of CLDN3 Moreover, the deprivation of -palmitoylation in CLDN3 significantly abolishes its tumorigenic promotion effect in ovarian cancer cells. By utilizing the co-immunoprecipitation assay, we further identify ZDHHC12 as a CLDN3-targating palmitoyltransferase from 23 ZDHHC family proteins. Furthermore, the knockdown of ZDHHC12 also significantly inhibits CLDN3 accurate membrane localization, protein stability and ovarian cancer cells tumorigenesis Thus, our work reveals -palmitoylation as a novel regulatory mechanism that modulates CLDN3 function, which implies that targeting ZDHHC12-mediated CLDN3 -palmitoylation might be a potential strategy for ovarian cancer therapy.
Полный текст:
1
База данных:
WPRIM
Язык:
En
Журнал:
Acta Pharmaceutica Sinica B
Год:
2020
Тип:
Article