| Structural highlights
Function
[HA11_MOUSE] Involved in the presentation of foreign antigens to the immune system. [E1A_ADE05] E1A protein has both transforming and trans-activating activities. Plays a role in viral genome replication by driving entry of quiescent cells into the cell cycle. Disrupts the function of host retinoblastoma protein RB1/pRb and isoform early E1A 26 kDa protein stabilizes TP53, which are key regulators of the cell cycle. Induces the disassembly of the E2F1 transcription factors from RB1 by direct competition for the same binding site on RB1, with subsequent transcriptional activation of E2F1-regulated S-phase genes. 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. Stimulation of progression from G1 to S phase allows the virus to efficiently use the cellular DNA replicating machinery to achieve viral genome replication. Interaction with RBX1 and CUL1 inhibits ubiquitination of the proteins targeted by SCF(FBW7) 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.[1] [2] [3] [4] [B2MG_MOUSE] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.
References
- ↑ Nakajima T, Morita K, Tsunoda H, Imajoh-Ohmi S, Tanaka H, Yasuda H, Oda K. Stabilization of p53 by adenovirus E1A occurs through its amino-terminal region by modification of the ubiquitin-proteasome pathway. J Biol Chem. 1998 Aug 7;273(32):20036-45. PMID:9685342
- ↑ Ledl A, Schmidt D, Muller S. Viral oncoproteins E1A and E7 and cellular LxCxE proteins repress SUMO modification of the retinoblastoma tumor suppressor. Oncogene. 2005 May 26;24(23):3810-8. PMID:15806172 doi:10.1038/sj.onc.1208539
- ↑ Isobe T, Hattori T, Kitagawa K, Uchida C, Kotake Y, Kosugi I, Oda T, Kitagawa M. Adenovirus E1A inhibits SCF(Fbw7) ubiquitin ligase. J Biol Chem. 2009 Oct 9;284(41):27766-79. Epub 2009 Aug 13. PMID:19679664 doi:M109.006809
- ↑ Yousef AF, Fonseca GJ, Pelka P, Ablack JN, Walsh C, Dick FA, Bazett-Jones DP, Shaw GS, Mymryk JS. Identification of a molecular recognition feature in the E1A oncoprotein that binds the SUMO conjugase UBC9 and likely interferes with polySUMOylation. Oncogene. 2010 Aug 19;29(33):4693-704. doi: 10.1038/onc.2010.226. Epub 2010 Jun, 14. PMID:20543865 doi:10.1038/onc.2010.226
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