Advances of structure and mechanisms of bromodomain-containing protein 4 and its related research in tumors / 生物工程学报

The bromodomain and extraterminal domain (Bet) family are the regulators of the epigenome and also the pivotal driving factors for the expression of tumor related genes that tumor cells depend on for survival and proliferation. Bromodomain-containing protein 4 (Brd4) is a member of the Bet protein family. Generally, Brd4 identifies acetylated histones and binds to the promoter or enhancer region of target genes to initiate and maintain expression of tumor related genes. Brd4 is closely related to the regulation of multiple transcription factors and chromatin modification and is involved in DNA damage repair and maintenance of telomere function, thus maintaining the survival of tumor cells. This review summarizes the structure and function of Brd4 protein and the application of its inhibitors in tumor research.

Oncogene-induced cellular senenscence / 基础医学与临床

Oncogene-induced senenscence(OIS) is defined as a stable proliferative arrest of normal cells upon overexpression of aberrant proliferative signals of oncogenes through MAPK and PI3K pathway.The molecular mechanism of OIS is related to the formation of heterochromatin and DNA-damage check-point response.The markers of OIS includ senescence-associated ?-galactosidase and senescence-associated heterochromatin foci.With the growing recognization of OIS,the new models of tumor progression are emerging.The further investigation on the mechanism of OIS is of great significance to understanding of the tumorigenesis and provide new ideas and methods of cancer treatment.

Cellular Responses to DNA Double Strand Breaks and Its Medical Significance / 生物化学与生物物理进展

The DNA damage response is a cornerstone of genomic stability.The cell utilizes mutiple mechanisms including damage detection,cell cycle regulation,damage repair and apoptosis to keep cell homeostasis.The DNA damage response include several biochemical pathways:first,the recognition and repair of damaged DNA;second,the activation of DNA damage checkpoint,which arrests cell cycle progression so as to provides time for DNA repair and prevention of the transmission of genomic abnormalities to the daughter cells;third,apoptosis,which eliminates serious damaged cells.The double strand break(DSB) is believed to be one of the most severe types of DNA damage,and errors in DSB repair could result in genomic instability that might lead to malignancy.It has been reported recently that constitutive activation of the ATM-Chk2-p53 pathway and phosphorylation of histone H2AX acts as an inducible anti-cancer barrier in the early stages of human tumorigenesis.This ATM-regulated DNA damage response network maintains genomic integrity and delays or prevents cancer by eliciting growth arrest or cell death.In context with a recent report,the ATM-dependent DNA-damage cellular signaling has also been shown to be involved in the integration of human immunodeficiency virus type-1(HIV-1) into host genomes,and KU55933,a specific ATM inhibitor,attenuated the infection of HIV-1 into host cells.The regulation and mechanisms of the signaling pathways of DSB response,and its role in HIV-1 infection and malignancy genesis were reviewed.