Arylsulfatase B regulates versican expression by galectin-3 and AP-1 mediated transcriptional effects.
Arylsulfatase B (N-acetylgalactosamine-4-sulfatase; ARSB) removes 4-sulfate groups from chondroitin-4-sulfate (C4S) and dermatan sulfate and is required for their degradation. In human prostate stromal and epithelial cells, when ARSB was silenced, C4S, versican and versican promoter activity increased, and the galectin-3 that co-immunoprecipitated with C4S declined. Galectin-3 silencing inhibited the ARSB-silencing-induced increases in versican and versican promoter due to effects on the AP-1-binding site in the versican promoter. These findings demonstrate for the first time the transcriptional mechanism whereby ARSB can regulate expression of an extracellular matrix proteoglycan with C4S attachments. In addition, following ARSB silencing, C4S that co-immunoprecipitated with versican increased, whereas co-immunoprecipitated EGFR declined, total EGFR increased and exogenous EGF-induced cell proliferation increased, suggesting profound effects of ARSB on vital cell processes.
1] Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA [2] Jesse Brown VA Medical Center, Chicago, IL, USA.
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Bhattacharyya
1] Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA [2] Jesse Brown VA Medical Center, Chicago, IL, USA.
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Feferman
1] Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA [2] Jesse Brown VA Medical Center, Chicago, IL, USA.
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Tobacman
D000595:Amino Acid Sequence; D000818:Animals; D001798:Blood Proteins; D045744:Cell Line, Tumor; D002809:Chondroitin Sulfates / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism*; D037161:Galectins; D015972:Gene Expression Regulation, Neoplastic; D016762:Genes, fos; D016758:Genes, jun; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D053675:Versicans / Q000235:genetics / Q000378:metabolism*
D001798:Blood Proteins; D037502:Galectin 3; D037161:Galectins; C428445:LGALS3 protein, human; C485095:Lgals3 protein, mouse; D018808:Transcription Factor AP-1; C508322:VCAN protein, human; C508323:Vcan protein, mouse; D053675:Versicans; D002809:Chondroitin Sulfates; C541485:EGFR protein, mouse; D066246:ErbB Receptors; D020051:N-Acetylgalactosamine-4-Sulfatase; C581941:ARSB protein, human