RESUMEN
The BRCA1 tumor suppressor protein heterodimerizes with its partner protein, BARD1, via the RING domain present in both proteins. The heterodimer contains an E3 ubiquitin ligase activity and participates in multiple cellular functions such as cell cycle control, DNA repair and regulation of gene transcription, collectively aimed at maintaining genomic stability and tumor suppression. Yet, the precise role of BRCA1 E3 ligase in these cellular functions is poorly understood. We present data showing that BRCA1 ubiquitinates G2/M cell cycle proteins, cyclin B and Cdc25C, leading to their accelerated degradation via a mechanism that is independent of APC/C. BRCA1-dependent degradation of cyclin B and Cdc25C is reversed by proteasome inhibitors and is enhanced following DNA damage, which may represent a possible mechanism to prevent cyclin B and Cdc25C accumulation, a requirement for mitotic entry. Our data provide mechanistic insight into how BRCA1 E3 ligase activity regulates the G2/M cell cycle checkpoint and, thus, contributes to maintenance of genomic stability.
Asunto(s)
Proteína BRCA1/metabolismo , Ciclina B/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Fosfatasas cdc25/metabolismo , Proteína BRCA1/genética , División Celular , Ciclina B/genética , Fase G2 , Técnicas de Silenciamiento del Gen , Inestabilidad Genómica , Humanos , Leupeptinas/farmacología , Células MCF-7/efectos de los fármacos , Células MCF-7/metabolismo , Inhibidores de Proteasoma/farmacología , Dominios y Motivos de Interacción de Proteínas , Dominios RING Finger , Enzimas Ubiquitina-Conjugadoras/metabolismo , Ubiquitinación , Fosfatasas cdc25/genéticaRESUMEN
Antibodies prepared against a peptide corresponding to the site of cyto-adherence of Mycoplasma genitalium adhesine inhibit or reduce the infectivity of the HIV-1BRU and HIV-2ROD strains of Human Immunodeficiency Virus in lymphoid cells. These results strengthen the hypothesis that some mycoplasmas may play an important part in HIV replication and pathogenicity.