title: UBLCP1 is a 26S proteasome phosphatase that regulates nuclear proteasome activity.
abstract: Protein degradation by the 26S proteasome is a fundamental process involved in a broad range of cellular activities, yet how proteasome activity is regulated remains poorly understood. We report here that ubiquitin-like domain-containing C-terminal domain phosphatase 1 (UBLCP1) is a 26S proteasome phosphatase that regulates nuclear proteasome activity. UBLCP1 directly interacts with the proteasome via its UBL domain and is exclusively localized in the nucleus. UBLCP1 dephosphorylates the 26S proteasome and inhibits proteasome activity in vitro. Knockdown of UBLCP1 in cells promotes 26S proteasome assembly and selectively enhances nuclear proteasome activity. Our results describe the first identified proteasome-specific phosphatase and uncover a unique mechanism for phosphoregulation of the proteasome.
authors.affiliation: Department of Pharmacology, University of California-San Diego, La Jolla, CA 92093-0721, USA.
authors.forename: Xing
authors.initials: X
authors.lastname: Guo
authors.forename: James L
authors.initials: JL
authors.lastname: Engel
authors.forename: Junyu
authors.initials: J
authors.lastname: Xiao
authors.forename: Vincent S
authors.initials: VS
authors.lastname: Tagliabracci
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Wang
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
authors.forename: Jack E
authors.initials: JE
authors.lastname: Dixon
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D004331:Drosophila melanogaster; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D008239:Lysine / Q000737:chemistry; D009687:Nuclear Proteins / Q000737:chemistry*; D010749:Phosphoprotein Phosphatases / Q000737:chemistry*; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry*; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: D009687:Nuclear Proteins; D010749:Phosphoprotein Phosphatases; C502029:UBLCP1 protein, human; D010744:Phosphoric Monoester Hydrolases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D008239:Lysine