DEPTOR is a stemness factor that regulates pluripotency of embryonic stem cells.
J Biol Chem
; 289(46): 31818-31826, 2014 Nov 14.
Article
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| MEDLINE
| ID: mdl-25258312
ABSTRACT
The mammalian target of rapamycin (mTOR) pathway regulates stem cell regeneration and differentiation in response to growth factors, nutrients, cellular energetics, and various extrinsic stressors. Inhibition of mTOR activity has been shown to enhance the regenerative potential of pluripotent stem cells. DEPTOR is the only known endogenous inhibitor of all known cellular mTOR functions. We show that DEPTOR plays a key role in maintaining stem cell pluripotency by limiting mTOR activity in undifferentiated embryonic stem cells (ESCs). DEPTOR levels dramatically decrease with differentiation of mouse ESCs, and knockdown of DEPTOR is sufficient to promote ESC differentiation. A strong decrease in DEPTOR expression is also observed during human ESCs differentiation. Furthermore, reduction in DEPTOR level during differentiation is accompanied by a corresponding increase in mTOR complex 1 activity in mouse ESCs. Our data provide evidence that DEPTOR is a novel stemness factor that promotes pluripotency and self-renewal in ESCs by inhibiting mTOR signaling.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Madre Pluripotentes
/
Péptidos y Proteínas de Señalización Intracelular
/
Células Madre Embrionarias
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2014
Tipo del documento:
Article