title: Ubiquitin-specific cysteine protease 2a (USP2a) regulates the stability of Aurora-A.
abstract: The ubiquitin/proteasome pathway plays critical roles in virtually all aspects of cell biology. Enzymes of the ubiquitin pathway add (ligases) or remove (deubiquitinases) ubiquitin tags to or from their target proteins in a selective fashion. USP2a is a member of a subfamily of deubiquitinases, called ubiquitin-specific cysteine proteases (USPs). Although USP2a has been reported to be a bona fide oncogene that regulates the stability of MDM2, MDMX, and FAS, it is likely that there are other unidentified substrates for USP2a. In this study, we show that USP2a mediates mitotic progression by regulating the stability of Aurora-A. Through cell-based screening of a USP siRNA library, we discovered that knockdown of USP2a reduced the protein levels of Aurora-A. USP2a interacts with Aurora-A directly in vitro and in vivo. In addition, Aurora-A is a substrate for USP2a in vitro and in vivo. Our study provides a novel mechanism for the role of USP2a in mediating the stability of Aurora-A.
authors: Cancer Research Department, Abbott Laboratories, Abbott Park, Illinois 60064, USA.
authors: Yan
authors: Y
authors: Shi
authors: Larry R
authors: LR
authors: Solomon
authors: Ana
authors: A
authors: Pereda-Lopez
authors: Vincent L
authors: VL
authors: Giranda
authors: Yan
authors: Y
authors: Luo
authors: Eric F
authors: EF
authors: Johnson
authors: Alexander R
authors: AR
authors: Shoemaker
authors: Joel
authors: J
authors: Leverson
authors: Xuesong
authors: X
authors: Liu
mesh_terms: D064127:Aurora Kinases; D010450:Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004795:Enzyme Stability / Q000502:physiology; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase
chemical_list: D025801:Ubiquitin; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D010450:Endopeptidases; C108665:USP2 protein, human; D043222:Ubiquitin Thiolesterase