title: The SUMO protease SENP6 is a direct regulator of PML nuclear bodies.
abstract: Promyelocytic leukemia protein (PML) is the core component of PML-nuclear bodies (PML NBs). The small ubiquitin-like modifier (SUMO) system (and, in particular, SUMOylation of PML) is a critical component in the formation and regulation of PML NBs. SUMO protease SENP6 has been shown previously to be specific for SUMO-2/3-modified substrates and shows preference for SUMO polymers. Here, we further investigate the substrate specificity of SENP6 and show that it is also capable of cleaving mixed chains of SUMO-1 and SUMO-2/3. Depletion of SENP6 results in accumulation of endogenous SUMO-2/3 and SUMO-1 conjugates, and immunofluorescence analysis shows accumulation of SUMO and PML in an increased number of PML NBs. Although SENP6 depletion drastically increases the size of PML NBs, the organizational structure of the body is not affected. Mutation of the catalytic cysteine of SENP6 results in its accumulation in PML NBs, and biochemical analysis indicates that SUMO-modified PML is a substrate of SENP6.
authors.affiliation: Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, DD15EH Scotland, United Kingdom.
authors.forename: Neil
authors.initials: N
authors.lastname: Hattersley
authors.forename: Linnan
authors.initials: L
authors.lastname: Shen
authors.forename: Ellis G
authors.initials: EG
authors.lastname: Jaffray
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Hay
mesh_terms: D020134:Catalytic Domain; D022003:Cell Nucleus Structures / Q000378:metabolism* / Q000648:ultrastructure; D002470:Cell Survival; D003545:Cysteine / Q000235:genetics; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D025841:Small Ubiquitin-Related Modifier Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D003546:Cysteine Endopeptidases; C408873:SENP6 protein, human; D003545:Cysteine