Identification of TAZ As a Binding Partner of the Polyomavirus T Antigens
Overview
Authors
Affiliations
A polyomavirus mutant isolated by the tumor host range selection procedure (19) has a three-amino-acid deletion (Delta2-4) in the common N terminus of the T antigens. To search for a cellular protein bound by wild-type but not the mutant T antigen(s), a yeast two-hybrid screen of a mouse embryo cDNA library was carried out with a bait of wild-type small T antigen (sT) fused N terminally to the DNA-binding domain of Gal4. TAZ, a transcriptional coactivator with a WW domain and PDZ-binding motif (17), was identified as a binding partner. TAZ bound in vivo to all three T antigens with different apparent affinities estimated as 1:7:100 (large T antigen [lT]:middle T antigen [mT]:sT). The Delta2-4 mutant T antigens showed no detectable binding. The sT and mT of the host range transformation-defective (hr-t) mutant NG59 with an alteration in the common sT/mT region (179 D-->NI) and a normal N terminus also failed to bind TAZ, while the unaltered lT bound but with reduced affinity compared to that seen in a wild-type virus infection. The WW domain but not the PDZ-binding motif of TAZ was essential for T antigen binding. The Delta2-4 mutant was defective in viral DNA replication. Forced overexpression of TAZ blocked wild-type DNA replication in a manner dependent on the binding site for the polyomavirus enhancer-binding protein 2alpha. Wild-type polyomavirus T antigens effectively block transactivation by TAZ. The functional significance of TAZ interactions with polyomavirus T antigens is discussed.
YAP1 activation by human papillomavirus E7 promotes basal cell identity in squamous epithelia.
Hatterschide J, Castagnino P, Kim H, Sperry S, Montone K, Basu D Elife. 2022; 11.
PMID: 35170430 PMC: 8959598. DOI: 10.7554/eLife.75466.
Shanzer M, Adler J, Ricardo-Lax I, Reuven N, Shaul Y Proc Natl Acad Sci U S A. 2017; 114(7):1678-1683.
PMID: 28154141 PMC: 5320963. DOI: 10.1073/pnas.1610223114.
Denis D, Rouleau C, Schaffhausen B J Virol. 2016; 91(2).
PMID: 27852846 PMC: 5215327. DOI: 10.1128/JVI.01774-16.
TAZ Induction Directs Differentiation of Thyroid Follicular Cells from Human Embryonic Stem Cells.
Ma R, Morshed S, Latif R, Davies T Thyroid. 2016; 27(2):292-299.
PMID: 27829313 PMC: 5912722. DOI: 10.1089/thy.2016.0264.
Rouleau C, Pores Fernando A, Hwang J, Faure N, Jiang T, White E J Virol. 2016; 90(16):7032-7045.
PMID: 27194756 PMC: 4984622. DOI: 10.1128/JVI.00417-16.