5zmc

Structural Basis for Reactivation of -146C>T Mutant TERT Promoter by cooperative binding of p52 and ETS1/2

spinqualitylabelsall models 5zmc, resolution 2.99Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5zmc is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.99Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ETS1_HUMAN Transcription factor. Publication Abstract from PubMed Transcriptional factors ETS1/2 and p52 synergize downstream of non-canonical NF-kappaB signaling to drive reactivation of the -146C>T mutant TERT promoter in multiple cancer types, but the mechanism underlying this cooperativity remains unknown. Here we report the crystal structure of a ternary p52/ETS1/-146C>T TERT promoter complex. While p52 needs to associate with consensus kappaB sites on the DNA to function during non-canonical NF-kappaB signaling, we show that p52 can activate the -146C>T TERT promoter without binding DNA. Instead, p52 interacts with ETS1 to form a heterotetramer, counteracting autoinhibition of ETS1. Analogous to observations with the GABPA/GABPB heterotetramer, the native flanking ETS motifs are required for sustained activation of the -146C>T TERT promoter by the p52/ETS1 heterotetramer. These observations provide a unifying mechanism for transcriptional activation by GABP and ETS1, and suggest that genome-wide targets of non-canonical NF-kappaB signaling are not limited to those driven by consensus kappaB sequences. Structural basis for reactivating the mutant TERT promoter by cooperative binding of p52 and ETS1.,Xu X, Li Y, Bharath SR, Ozturk MB, Bowler MW, Loo BZL, Tergaonkar V, Song H Nat Commun. 2018 Aug 9;9(1):3183. doi: 10.1038/s41467-018-05644-0. PMID:30093619 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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