TRAF4 Promotes Fibroblast Proliferation in Keloids by Destabilizing p53 via Interacting with the Deubiquitinase USP10.
J Invest Dermatol
; 139(9): 1925-1935.e5, 2019 09.
Article
en En
| MEDLINE
| ID: mdl-30940456
Keloids represent one extreme of aberrant dermal wound healing. One of the important characteristics of keloids is uncontrolled fibroblasts proliferation. However, the mechanism of excessive proliferation of fibroblasts in keloids remains elusive. In this study, we demonstrated that TRAF4 was highly expressed in keloid fibroblasts and promoted fibroproliferation. We investigated the underlying molecular mechanism and found that TRAF4 suppressed the p53 pathway independent of its E3 ubiquitin ligase activity. Specifically, TRAF4 interacted with the deubiquitinase USP10 and blocked the access of p53 to USP10, resulting in p53 destabilization. Knockdown of p53 rescued cell proliferation in TRAF4-knockdown keloid fibroblasts, suggesting that the regulation of proliferation by TRAF4 in keloids relied on p53. Furthermore, in keloid patient samples, TRAF4 expression was inversely correlated with p53-p21 signaling activity. These findings help to elucidate the mechanisms underlying keloid development and indicate that blocking TRAF4 could represent a potential strategy for keloid therapy in the future.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteína p53 Supresora de Tumor
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Ubiquitina Tiolesterasa
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Factor 4 Asociado a Receptor de TNF
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Fibroblastos
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Queloide
Límite:
Adolescent
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Adult
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Child
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Female
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Humans
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Male
Idioma:
En
Revista:
J Invest Dermatol
Año:
2019
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos