Biomaterial Database

Adenovirus E1A proteins induce apoptosis by both p53-dependent and p53-independent mechanisms. 1995

J G Teodoro, and G C Shore, and P E Branton

Department of Biochemistry, McGill University, Montréal, Quebec, Canada.

E1A of human adenovirus type 5 (Ad5) encodes proteins of 289 and 243 residues (289R and 243R) which differ only by the 46 amino acid CR3 region known to activate expression of certain cellular and early viral genes. E1A proteins also induce DNA synthesis and cell transformation, but as well can stimulate apoptosis. Two adenovirus E1B products act to protect cells from E1A-induced cell death, including a 19 kDa protein which is functionally similar to the cellular Bcl-2 suppressor of apoptosis, and a 55 kDa species which binds to and inhibits p53. Previous studies suggested that E1A-induced cell death occurs via a p53-dependent mechanism requiring regions of E1A proteins linked to induction of DNA synthesis and cell transformation. We report here that the 289R E1A protein induces apoptosis in cell lines lacking p53, whereas the 243R product was dependent upon p53. We also show that this p53-independent process involves the expression of one or more additional viral proteins which are presumably synthesized in response to transactivation by 289R. Thus E1A proteins induce cell death by both p53-dependent and p53-independent mechanisms involving separate E1A functions.

UI	MeSH Term	Description	Entries
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D004249	DNA Damage	Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.	DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D016158	Genes, p53	Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.	Genes, TP53,TP53 Genes,p53 Genes,Gene, TP53,Gene, p53,TP53 Gene,p53 Gene
D016159	Tumor Suppressor Protein p53	Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.	p53 Tumor Suppressor Protein,Cellular Tumor Antigen p53,Oncoprotein p53,TP53 Protein,TRP53 Protein,p53 Antigen,pp53 Phosphoprotein,Phosphoprotein, pp53
D017209	Apoptosis	A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.	Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D017500	Adenovirus E1A Proteins	Proteins transcribed from the E1A genome region of ADENOVIRUSES which are involved in positive regulation of transcription of the early genes of host infection.	Adenovirus E1A Protein Domain 3,Adenovirus E1A Protein,E1A Protein, Adenovirus,E1A Proteins, Adenovirus
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D066298	In Vitro Techniques	Methods to study reactions or processes taking place in an artificial environment outside the living organism.	In Vitro Test,In Vitro Testing,In Vitro Tests,In Vitro as Topic,In Vitro,In Vitro Technique,In Vitro Testings,Technique, In Vitro,Techniques, In Vitro,Test, In Vitro,Testing, In Vitro,Testings, In Vitro,Tests, In Vitro,Vitro Testing, In