Tax1BP1 interacts with papillomavirus E2 and regulates E2-dependent transcription and stability.
The papillomavirus E2 proteins regulate viral replication, gene transcription, and genome maintenance by interacting with other viral and host proteins. From a yeast two-hybrid screen, we identified the cellular protein Tax1BP1 as a novel binding partner of human papillomavirus type 18 (HPV18) E2. Tax1BP1 also interacts with the HPV16 and bovine papillomavirus type 1 (BPV1) E2 proteins, with the C-terminal region of Tax1BP1 interacting with the N-terminal transactivation domain of BPV1 E2. Tax1BP1 complexes with p300 and acts synergistically as a coactivator with p300 to enhance E2-dependent transcription. Using chromatin immunoprecipitation assays, we show that Tax1BP1 and E2 localize to the long control region on the BPV1 genome. Tax1BP1 was recently reported to bind ubiquitin and to function as an essential component of an A20 ubiquitin-editing complex. We demonstrate that Tax1BP1 plays a role in the regulation of the steady-state level of E2 by preventing its proteasomal degradation. These studies provide new insights into the regulation of E2 functions.
Wang
Xiaoyu
X
Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Naidu
Samisubbu R
SR
Sverdrup
Francis
F
Androphy
Elliot J
EJ
D000818:Animals; D052688:Bovine papillomavirus 1 / Q000235:genetics / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D052140:Human papillomavirus 11 / Q000235:genetics / Q000378:metabolism; D052161:Human papillomavirus 18 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism; D027383:Papillomaviridae / Q000235:genetics* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D055550:Protein Stability; D034741:RNA, Small Interfering; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques; D054875:Ubiquitination; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C051550:E2 protein, Bovine papillomavirus; C054855:E2 protein, Human papillomavirus type 16; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D009856:Oncogene Proteins, Viral; D034741:RNA, Small Interfering; C120635:TAX1BP1 protein, human; D014764:Viral Proteins; D046988:Proteasome Endopeptidase Complex