4nbp

Structural highlights

Function

LT_POVJC Isoform large T antigen is a key early protein essential for both driving viral replication and inducing cellular transformation. Plays a role in viral genome replication by driving entry of quiescent cells into the cell cycle and by autoregulating the synthesis of viral early mRNA. Displays highly oncogenic activities by corrupting the host cellular checkpoint mechanisms that guard cell division and the transcription, replication, and repair of DNA. Participates in the modulation of cellular gene expression preceeding viral DNA replication. This step involves binding to host key cell cycle regulators retinoblastoma protein RB1/pRb and TP53. Induces the disassembly of host E2F1 transcription factors from RB1, thus promoting transcriptional activation of E2F1-regulated S-phase genes. Inhibits host TP53 binding to DNA, abrogating the ability of TP53 to stimulate gene expression. Plays the role of a TFIID-associated factor (TAF) in transcription initiation for all three RNA polymerases, by stabilizing the TBP-TFIIA complex on promoters. Initiates viral DNA replication and unwinding via interactions with the viral origin of replication. Binds two adjacent sites in the SV40 origin. The replication fork movement is facilitated by Large T antigen helicase activity. Activates the transcription of viral late mRNA, through host TBP and TFIIA stabilization. Interferes with histone deacetylation mediated by HDAC1, leading to activation of transcription (By similarity).

See Also

• Large T Antigen

References

1. ↑ Meinke G, Phelan PJ, Kalekar R, Shin J, Archambault J, Bohm A, Bullock PA. Insights into the initiation of JC virus DNA replication derived from the crystal structure of the T-antigen origin binding domain. PLoS Pathog. 2014 Feb 20;10(2):e1003966. doi: 10.1371/journal.ppat.1003966., eCollection 2014 Feb. PMID:24586168 doi:http://dx.doi.org/10.1371/journal.ppat.1003966