RESUMO
The c-myc protooncogene product (c-Myc) is a transcription factor and is rapidly induced in resting cells following various mitogenic stimuli. c-Myc is thus suggested to play an important role in the transition from quiescence to proliferation. Despite numerous studies, including those on the connection between cyclin E/cyclin-dependent kinase 2 and c-Myc, little has been clarified about c-Myc in terms of the cell cycle regulation. Here we show that c-Myc can directly bind to the carboxyl-terminal region of the cyclin-dependent kinase inhibitor p21(cip1/waf1/sdi1) and thus partially relieves the p21 of the inhibitory effect on DNA synthesis directed by the proliferating cell nuclear antigen-dependent DNA polymerase delta. As for transcription, on the other hand, the p21 binding to the Myc box II region of c-Myc blocks c-Myc-Max complex formation on the E-box and thereby suppresses the transcriptional activation from the E-box by c-Myc. These results suggest that c-Myc activates DNA replication via inactivation of p21 and that p21, vice versa, represses the transcriptional activity of c-Myc. The balance of the reciprocal inactivation between c-Myc and p21 may determine the course of cellular processes such as cell proliferation, differentiation, and apoptosis.
Assuntos
Ciclinas/metabolismo , Replicação do DNA , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transcrição Gênica , Sítios de Ligação , Ligação Competitiva , Clonagem Molecular , Inibidor de Quinase Dependente de Ciclina p21 , Ciclinas/isolamento & purificação , Inibidores Enzimáticos/metabolismo , Escherichia coli , Genes myc , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteínas Proto-Oncogênicas c-myc/química , Proteínas Proto-Oncogênicas c-myc/isolamento & purificação , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismoRESUMO
A retrospective study was made of the clinical features, especially oesophageal varices, of 93 patients with PBC. The 5 year survival rate of asymptomatic PBC patients was 88.7% and that of symptomatic PBC was 43.7%. The 5 year survival rate of the group with oesophageal varices was 44.0% and that of the group without varices was 68.8%. The 5 year survival rate of the patients with high-risk varices was 39.1% and of those without high-risk varices was 67.9%. Management of variceal bleeding in PBC patients was considered very difficult. In prognostic study, the patients with the prophylactic therapy were better than the patients with emergency or elective therapy. The antiM8 (a subtype of antimitochondrial antibody) positive patients had poor prognosis compared with antiM8 negative patients. Therefore, it was concluded from these data that some kind of treatment was necessary for patients with high-risk varices. In particular, it was considered necessary to monitor closely the patients whose serum alkaline phosphatase levels had remained high.
