FEATURES

FAMILY

DESCRIPTION

Also known as E1A_ADE05, E1A. Plays a role in viral genome replication by driving entry of quiescent cells into the cell cycle. Stimulation of progression from G1 to S phase allows the virus to efficiently use the cellular DNA replicating machinery to achieve viral genome replication. E1A protein has both transforming and trans-activating activities. Induces the disassembly of the E2F1 transcription factor from RB1 by direct competition for the same binding site on RB1, with subsequent transcriptional activation of E2F1-regulated S-phase genes and of the E2 region of the adenoviral genome. Release of E2F1 leads to the ARF-mediated inhibition of MDM2 and causes TP53/p53 to accumulate because it is not targeted for degradation by MDM2-mediated ubiquitination anymore. This increase in TP53, in turn, would arrest the cell proliferation and direct its death but this effect is counteracted by the viral protein E1B-55K. Inactivation of the ability of RB1 to arrest the cell cycle is critical for cellular transformation, uncontrolled cellular growth and proliferation induced by viral infection. Interaction with RBX1 and CUL1 inhibits ubiquitination of the proteins targeted by SCF(FBXW7) ubiquitin ligase complex, and may be linked to unregulated host cell proliferation. The tumorigenesis-restraining activity of E1A may be related to the disruption of the host CtBP-CtIP complex through the CtBP binding motif. Interaction with host TMEM173/STING impairs the ability of TMEM173/STING to sense cytosolic DNA and promote the production of type I interferon (IFN-alpha and IFN-beta) (PubMed:26405230). Promotes the sumoylation of host ZBED1/hDREF with SUMO1 (PubMed:25210186). Interacts with host UBE2I; this interaction interferes with polySUMOylation (Probable) (PubMed:8824223, PubMed:20543865). Interacts with host RB1; this interaction induces the aberrant dissociation of RB1-E2F1 complex thereby disrupting the activity of RB1 and activating E2F1-regulated genes (PubMed:17974914). Interacts with host ATF7; the interaction enhances ATF7-mediated viral transactivation activity which requires the zinc binding domains of both proteins (By similarity). Isoform early E1A 32 kDa protein and isoform early E1A 26 kDa protein interact (via N-terminus) with CUL1 and E3 ubiquitin ligase RBX1; these interactions inhibit RBX1-CUL1-dependent elongation reaction of ubiquitin chains and attenuate ubiquitination of SCF(FBXW7) target proteins (PubMed:19679664). Interacts (via PXLXP motif) with host ZMYND11/BS69 (via MYND-type zinc finger); this interaction inhibits E1A mediated transactivation (PubMed:11733528). Interacts with host EP300; this interaction stimulates the acetylation of RB1 by recruiting EP300 and RB1 into a multimeric-protein complex (PubMed:11433299). Interacts with host CTBP1 and CTBP2; this interaction seems to potentiate viral replication (PubMed:23747199, PubMed:7479821). Interacts with host DCAF7 (ref.16). Interacts with host DYRK1A (PubMed:23864635). Interacts with host KPNA4; this interaction allows E1A import into the host nucleus (PubMed:23864635). Interacts with host EP400; this interaction stabilizes MYC (PubMed:18413597). Interacts with host TBP protein; this interaction probably disrupts the TBP-TATA complex (PubMed:8146144). Interacts (via LXCXE motif) with host TMEM173/STING; this interaction impairs the ability of TMEM173/STING to sense cytosolic DNA and promote the production of type I interferon (IFN-alpha and IFN-beta) (PubMed:26405230). Interacts (via C-terminus) with host ZBED1/hDREF (via C-terminus); the interaction is direct (PubMed:25210186).

EXTERNAL LINKS

E1A

Early E1A protein

E1A

Molecular Synopsis