title: The ubiquitin-specific peptidase USP15 regulates human papillomavirus type 16 E6 protein stability.
abstract: Proteomic identification of human papillomavirus type 16 (HPV16) E6-interacting proteins revealed several proteins involved in ubiquitin-mediated proteolysis. In addition to the well-characterized E6AP ubiquitin-protein ligase, a second HECT domain protein (HERC2) and a deubiquitylating enzyme (USP15) were identified by tandem affinity purification of HPV16 E6-associated proteins. This study focuses on the functional consequences of the interaction of E6 with USP15. Overexpression of USP15 resulted in increased levels of the E6 protein, and the small interfering RNA-mediated knockdown of USP15 decreased E6 protein levels. These results implicate USP15 directly in the regulation of E6 protein stability and suggest that ubiquitylated E6 could be a substrate for USP15 ubiquitin peptidase activity. It remains possible that E6 could affect the activity of USP15 on specific cellular substrates, a hypothesis that can be tested as more is learned about the substrates and pathways controlled by USP15.
authors: Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors: Robin M
authors: RM
authors: Vos
authors: Jennifer
authors: J
authors: Altreuter
authors: Elizabeth A
authors: EA
authors: White
authors: Peter M
authors: PM
authors: Howley
mesh_terms: D002460:Cell Line; D010450:Endopeptidases / Q000235:genetics / Q000502:physiology*; D055785:Gene Knockdown Techniques / Q000379:methods; D020868:Gene Silencing; D054884:Host-Pathogen Interactions; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D055550:Protein Stability; D012097:Repressor Proteins / Q000378:metabolism*; D064570:Ubiquitin-Specific Proteases
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D010450:Endopeptidases; C579226:USP15 protein, human; D064570:Ubiquitin-Specific Proteases