RESUMO
While studies have highlighted the role of HOXA9-13 and PBX1 homeobox genes during the development of the female genital tract, the molecular mechanisms triggered by these genes are incompletely elucidated. In several developmental pathways, PBX1 binds to MEINOX family members in the cytoplasm to be imported into the nucleus where they associate with HOX proteins to form a higher complex that modulates gene expression. This concept has been challenged by a recent report showing that in some cell cultures, PBX1 nuclear localization might be regulated independently of MEINOX proteins (Kilstrup-Nielsen et al., 2003). Our work gives the first illustration of this alternative mechanism in an organogenesis process. Indeed, we show that PBX1 is mostly cytoplasmic in epithelial endometrial cells of the developing female genital tract despite the nuclear localization of MEIS1. We thus provide evidence for a control of PBX1 intracellular distribution which is independent of MEINOX proteins, but is cell cycle correlated.
Assuntos
Células Epiteliais/metabolismo , Genitália Feminina/embriologia , Genitália Feminina/metabolismo , Proteínas de Homeodomínio/metabolismo , Proteínas de Neoplasias/metabolismo , Fatores de Transcrição/metabolismo , Animais , Ciclo Celular , Linhagem Celular , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Células Epiteliais/citologia , Feminino , Regulação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Genitália Feminina/citologia , Proteínas de Homeodomínio/genética , Humanos , Camundongos , Proteína Meis1 , Proteínas de Neoplasias/genética , Fator de Transcrição 1 de Leucemia de Células Pré-B , Transporte Proteico , Fatores de Transcrição/genéticaRESUMO
Multiple sclerosis is a chronic inflammatory disease of the central nervous system with a genetic component. Until now, the more consistent association with the disease is found with the major histocompatibility complex, especially HLA-DRB1*1501-DQB1*0602 haplotype. In this report, we demonstrate the interaction of Cytotoxic T Lymphocyte-associated antigen 4 (CTLA-4 [CD152]) gene with DRB1*15 haplotype in multiple sclerosis genetic susceptibility. Our data were obtained from two European independent family-based studies including 610 multiple sclerosis family trios. Ann Neurol 2003;54:119-122
