Muscle regulatory factor MRF4 activates differentiation in rhabdomyosarcoma RD cells through a positive-acting C-terminal protein domain.
Oncogene
; 22(36): 5658-66, 2003 Aug 28.
Article
en En
| MEDLINE
| ID: mdl-12944914
ABSTRACT
Rhabdomyosarcoma (RMS) has deregulated proliferation and is blocked in the differentiation program despite Myf-5, MyoD and myogenin expression. Here we show that ectopic expression of MRF4, which is not subject to an autoregulatory pathway but regulated by the other MRFs protein family, induces growth arrest and terminal differentiation in RD cells. Deletion mapping identified a positive-acting C-terminal domain in MRF4 as the mediator of transcriptional activity, revealing a conserved motif with helix III in MyoD previously found to initiate expression of endogenous skeletal muscle genes. By using chimeric MyoD/MRF4 proteins, we observe that the C-terminal motif of MRF4 rescues MyoD activity in RD cells. Moreover, comparative induction of muscle-specific genes following activation of MyoD, through the expression of a constitutively activated MKK6 either in the absence or presence of MRF4, shows that MyoD and MRF4 can differently regulate muscle genes expression. Together, these results demonstrate that the MRF4 C-terminus functions as specification as well as activation domain in tumor cells. They provide a basis to identify gene products necessary for b-HLH-mediated differentiation versus tumor progression.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Rabdomiosarcoma
/
Diferenciación Celular
/
Factores Reguladores Miogénicos
/
Músculos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Oncogene
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2003
Tipo del documento:
Article
País de afiliación:
Francia