title: The co-chaperone DNAJC12 binds to Hsc70 and is upregulated by endoplasmic reticulum stress.
abstract: Human DNAJC12 is a J domain-containing protein whose regulation, subcellular localization, and function are currently unknown. We show here that the abundance of DNAJC12 in human LNCaP prostate cancer cells is upregulated by the stress-inducing drug A23187 and by the stressregulated transcription factor AIbZIP/CREB3L4. The DNAJC12 gene encodes two isoforms, only one of which (isoform a) is expressed in these cells. Immunofluorescence studies showed that a recombinant DNAJC12 protein is diffusely distributed in the cytoplasm. To identify substrates of DNAJC12, we used an immunoaffinity-mass spectrometry approach in cells that express epitope-tagged DNAJC12. The list of potential DNAJC12-binding proteins that were identified in this screen includes several nucleotide-binding proteins. The most frequently identified partner of DNAJC12 in unstressed cells was Hsc70, a cognate Hsp70 chaperone, whereas in stressed cells, the ER chaperone BiP was frequently associated with DNAJC12. Immunoprecipitation experiments confirmed that the endogenous DNAJC12 and Hsc70 proteins interact in LNCaP cells. These results clarify the role of DNAJC12 in the regulation of Hsp70 function.
authors.forename: Jin
authors.initials: J
authors.lastname: Choi
authors.forename: Sonia
authors.initials: S
authors.lastname: Djebbar
authors.forename: Andréa
authors.initials: A
authors.lastname: Fournier
authors.forename: Claude
authors.initials: C
authors.lastname: Labrie
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D009687:Nuclear Proteins / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D011506:Proteins / Q000378:metabolism*; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C448322:CREB3L4 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D050883:HSC70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D009687:Nuclear Proteins; D011506:Proteins; D000001:Calcimycin