E1A is a transforming viral protein produced by adenovirus. E1A forces cells through the restriction point of the cell cycle into the S phase by forming complexes with Rb and CBP/p300. By binding Rb it activates E2F, and by binding CBP it activates its histone acetyltransferase activity, both inducing S-phase-gene expression. E1A has transforming activity only when cell proliferation is not blocked, e.g. by p53. E1A stimulated proliferation normally would trigger p53-dependent cell cycle arrest what results in apoptosis. For that reason, adenovirus additionally expresses E1B which blocks p53 function.
E1B (55 kDa) is an adenovirus oncogene, which blocks the function of p53. E1B 55kDa does not affect DNA binding but interferes with the transactivational function of p53.
E1B19k is an anti-apoptotic adenovirus protein, which indirectly prevents Fas-mediated activation of caspase-8, possibly by its interaction with FLASH. E1B19k also has been described as a general inhibitor of both p53-dependent and -independent cell death. E1B 19kDa contains regions that are related to BH1 and BH3 domains of Bcl-2 and mediate interactions with Bax (but also BIK and BAK), suggesting that Bax-E1B19K establishes an apoptotic control set point that is analogous to that of Bax-Bcl-2 (Cheng, 1996, JBC, 271(39): 24221).
E2F is a family of key transcription factors for S-phase-gene induction. E2F has binding sites in the promoters of many of the genes that are involved in cell- cycle progression. E2F is strictly regulated during the cell cycle: it is inactive when bound in a complex with the Rb protein.
Viral onogenes produced by papillomavirus: E6 inactivates Rb, while E7 inactivates p53.
E6-Associated Protein (E6-AP) and papilloma virus E6 protein together form a complex that functions as a p53-specific E3 ubiquitin ligase, resulting in ubiquitin-proteasome-dependent proteolysis of p53. E6-AP contains the HECT domain (Homologous to E6-AP Carboxy Terminus) which among others contains the catalytic site cystein residue for ubiquitin ligase activity. Interestingly, mutations in the E6-AP gene cause Angelman syndrome. Among others, E6-AP ubiquitinates the tyrosine kinases Blk and Src. E6-AP undergoes E6-dependent autoubiquitination (Pickart, 2001, Annu. Rev. Biochem. 70: 503-33).
EGg Laying defective 1 (EGL-1) was identified by gain-of-function mutations in C.elegans causing the HSN neurons to undergo programmed cell death. By contrast,a loss-of-function egl-1 mutation prevents most if not all somatic PCD. Egl-1 is a pro-apoptotic Bcl-2 family member in C. elegans. It negatively regulates ced-9, which protects against various kinds of death in C.elegans and is a member of the Bcl-2 family. Egl-1 contains a 9 amino acids region similar to the BH3 domain but does not contain BH1, BH2, or BH4 domains. Egl-1 was proposed to activate PCD by binding to and directly inhibiting the activity of ced-9, and thus releasing the cell death activator ced-4 from a ced-9/ced-4-containing protein complex (Conradt and Horvitz, 1998, Cell, 93: 519-529).
Electrophoretic Mobility Shift Assay
Endonuclease G (30 kDa) is a mitochondria-specific nuclease that translocates into the nucleus during apoptosis. Endo G most likely co-localizes with cytochrome c in the inner membrane space. Once released from the mitochondria, endo G cleaves chromatin DNA into nucleosomal fragments independently of caspases. Therefore, endo G represents a caspase-independent apoptotic pathway initiated from the mitochondria. Cps-6 is the C.elegans homologue of human endo G (Li et al., 2001, Nature, 412: 95-99).
Extracellular Receptor-activated Kinases-1 and -2, prototypic MAPKs implicated in cell cycle entry.
Embryonic Stem cells .
Etoposide is a topoisomerase II inhibitor, inducing apoptosis in a p53-dependent manner (Lowe et al., 1993, Nature 362: 847; Clarke et al., 1993, Nature 362: 849).
Ewing's sarcoma is a cancer in the marrow of the midshaft of the bone, most commonly in the thighbone, shinbone, and upper arm. It is a rare cancer that occurs most frequently in children and young adults.
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