RESUMO
Many studies showed that the p300/CBP coactivator is limiting. Here we review three studies that showed how transcription complexes formed on viral cis-regulator elements compete with cellular transcription complexes by sequestrating the p300/CBP coactivator. According to the microcompetition model, this sequestering can cause disease. We use the microcompetition model to explain how a specific type of sequestering, caused by a latent virus that has an active cis-regulatory element in its promoter/enhancer that binds the transcription complex p300/CBP ·GABP can cause diseases such as cancer, atherosclerosis, diabetes, and certain autoimmune diseases.
Assuntos
Regulação da Expressão Gênica/fisiologia , Papillomavirus Humano 18/fisiologia , Sequências Reguladoras de Ácido Nucleico/fisiologia , Fatores de Transcrição de p300-CBP/metabolismo , Regulação da Expressão Gênica/imunologia , Humanos , Regiões Promotoras Genéticas , Fatores de Transcrição de p300-CBP/genéticaRESUMO
Most breast cancer cases show a decrease in the concentration of the breast cancer type 1 susceptibility protein (BRCA1). However, only a small portion of these cases have a mutated BRCA1 gene. Although many attempts have been made to identify the reason for the decrease in BRCA1 concentration in sporadic, non-heritable breast cancer cases, the cause is still unknown. In this review, we use the Microcompetition Model to explain how certain latent viruses, which are frequently detected in breast cancer tumors, can decrease the expression of the BRCA1 gene and cause the development of breast tumors.
Assuntos
Neoplasias da Mama/etiologia , Latência Viral/fisiologia , Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/virologia , Regulação para Baixo , Feminino , Fator de Transcrição de Proteínas de Ligação GA/metabolismo , Genes BRCA1 , Humanos , Modelos Biológicos , Retroviridae/isolamento & purificação , Retroviridae/patogenicidadeRESUMO
CBP and p300 are histone acetyltransferase coactivators that control the transcription of numerous genes in humans, viruses, and other organisms. Although two separate genes encode CBP and p300, they share a 61% sequence identity, and they are often mentioned together as p300/CBP. Zhou et al. showed that under hypoxic conditions, HIF1α and the tumor suppressor p53 compete for binding to the limiting p300/CBP coactivator. Jethanandani & Kramer showed that δEF1 and MYOD genes compete for the limited amount of p300/CBP in the cell. Bhattacharyya et al. showed that the limiting availability of p300/CBP in the cell serves as a checkpoint for HIF1α activity. Here, we use the microcompetition model to explain how latent viruses with a specific viral cis-regulatory element in their promoter/enhancer can disrupt this competition, causing diseases such as cancer, diabetes, atherosclerosis, and obesity.