Biomaterial Database

The transcriptional cofactor MCAF1/ATF7IP is involved in histone gene expression and cellular senescence. 2013

Nobuhiro Sasai, and Noriko Saitoh, and Hisato Saitoh, and Mitsuyoshi Nakao

Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.

Cellular senescence is post-mitotic or oncogene-induced events combined with nuclear remodeling. MCAF1 (also known as hAM or ATF7IP), a transcriptional cofactor that is overexpressed in various cancers, functions in gene activation or repression, depending on interacting partners. In this study, we found that MCAF1 localizes to PML nuclear bodies in human fibroblasts and non-cancerous cells. Interestingly, depletion of MCAF1 in fibroblasts induced premature senescence that was characterized by cell cycle arrest, SA-β-gal activity, and senescence-associated heterochromatic foci (SAHF) formation. Under this condition, core histones and the linker histone H1 significantly decreased at both mRNA and protein levels, resulting in reduced nucleosome formation. Consistently, in activated Ras-induced senescent fibroblasts, the accumulation of MCAF1 in PML bodies was enhanced via the binding of this protein to SUMO molecules, suggesting that sequestration of MCAF1 to PML bodies promotes cellular senescence. Collectively, these results reveal that MCAF1 is an essential regulator of cellular senescence.

UI	MeSH Term	Description	Entries
D009687	Nuclear Proteins	Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.	Nucleolar Protein,Nucleolar Proteins,Nuclear Protein,Protein, Nuclear,Protein, Nucleolar,Proteins, Nuclear,Proteins, Nucleolar
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D012097	Repressor Proteins	Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.	Repressor Molecules,Transcriptional Silencing Factors,Proteins, Repressor,Silencing Factors, Transcriptional
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006657	Histones	Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.	Histone,Histone H1,Histone H1(s),Histone H2a,Histone H2b,Histone H3,Histone H3.3,Histone H4,Histone H5,Histone H7
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071156	Promyelocytic Leukemia Protein	A tripartite motif protein that contains three ZINC FINGERS, including a RING FINGER DOMAIN, at its N-terminal. Several nuclear and one cytoplasmic isoforms result from alternative splicing of the PML gene; most nuclear isoforms localize to subnuclear structures (PML nuclear bodies) that are disrupted in ACUTE PROMYELOCYTIC LEUKEMIA cells.	RNF71 Protein,TRIM19 Protein
D014157	Transcription Factors	Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.	Transcription Factor,Factor, Transcription,Factors, Transcription
D014452	Ubiquitins	A family of proteins that are structurally-related to Ubiquitin. Ubiquitins and ubiquitin-like proteins participate in diverse cellular functions, such as protein degradation and HEAT-SHOCK RESPONSE, by conjugation to other proteins.	Ubiquitin-Like Protein,Ubiquitin-Like Proteins,Protein, Ubiquitin-Like,Proteins, Ubiquitin-Like,Ubiquitin Like Protein,Ubiquitin Like Proteins