title: Oncogenic acidic nuclear phosphoproteins ANP32C/D are novel clients of heat shock protein 90.
abstract: The acidic nuclear phosphoproteins (ANP32A-H) are an evolutionarily conserved family of proteins with diverse and sometimes opposing cellular functions. Here we show that the oncogenic family members ANP32C and ANP32D are associated in complexes containing the molecular chaperone Hsp90. The oncogenic ANP32C protein appears to be highly unstable with a rapid degradation (t1/2>30 min) occurring upon treatment of cells with cycloheximide. ANP32C was also found to be associated with oncogenic Hsp90 complexes by virtue of its ability to interact and be immunoprecipitated by the Hsp90 inhibitor PU-H71. Further studies treating cells with the Hsp90 inhibitors PU-H71 and 17-AAG showed atypical increased protein stability and prevention of ANP32C degradation compared to the Hsp90 client AKT. Cells overexpressing ANP32C or its mutant ANP32CY140H showed enhanced sensitivity to treatment with PU-H71 as demonstrated by CCK-8 and colony formation assays. Our results highlight that certain malignancies with ANP32C/D overexpression or mutation might be specifically targeted using Hsp90 inhibitors.
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
authors.forename: Yuliia
authors.initials: Y
authors.lastname: Yuzefovych
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Blasczyk
authors.affiliation: Institute for Transfusion Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. Electronic address: huyton.trevor@mh-hannover.de.
authors.forename: Trevor
authors.initials: T
authors.lastname: Huyton
mesh_terms: D019943:Amino Acid Substitution; D052117:Benzodioxoles / Q000494:pharmacology; D002460:Cell Line; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability / Q000187:drug effects; D059748:Proteolysis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D011687:Purines / Q000494:pharmacology
chemical_list: C489949:ANP32C protein, human; D052117:Benzodioxoles; D018841:HSP90 Heat-Shock Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011687:Purines; C526550:9H-purine-9-propanamine, 6-amino-8-((6-iodo-1,3-benzodioxol-5-yl)thio)-N-(1-methylethyl)-; D051057:Proto-Oncogene Proteins c-akt
keywords: ANP32C; Cancer; Cell cycle; Hsp90