biostudies-literatureBhattacharyya SUniversity of Illinois at Urbana-ChampaignUS Department of Veterans Affairs110402https://www.ebi.ac.uk/biostudies/studies/S-EPMC12301740biostudies-literatureUnknown301(8)Previous experiments in the syngeneic, murine, and subcutaneous model of malignant melanoma and human melanoma cells showed that treatment by recombinant human (rh) Arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfatase) markedly reduced the volume of tumors, improved survival, and inhibited invasiveness. In this report, the impact of ARSB on the progression of metastatic, pulmonary B16F10 melanomas in C57BL/6J mice is addressed, and the underlying apoptotic mechanism by which ARSB inhibits melanoma growth is identified. Exogenous ARSB, which has mannose 6-phosphate attachments, acts through insulin-like growth factor 2 receptor (IGF2R), a cation-independent mannose-6-phosphate receptor, and increases expression of constitutive photomorphogenic protein (COP)1. Expression of COP1, an E3 uThe Journal of biological chemistryArylsulfatase B induces melanoma apoptosis by the ubiquitin ligase COP1.PMC12301740BX-00534261802Zhang FYang JBhattacharyya SO-Sullivan IWhiteley HETobacman JKfalseArylsulfatase B induces melanoma apoptosis by the ubiquitin ligase COP1.Previous experiments in the syngeneic, murine, and subcutaneous model of malignant melanoma and human melanoma cells showed that treatment by recombinant human (rh) Arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfatase) markedly reduced the volume of tumors, improved survival, and inhibited invasiveness. In this report, the impact of ARSB on the progression of metastatic, pulmonary B16F10 melanomas in C57BL/6J mice is addressed, and the underlying apoptotic mechanism by which ARSB inhibits melanoma growth is identified. Exogenous ARSB, which has mannose 6-phosphate attachments, acts through insulin-like growth factor 2 receptor (IGF2R), a cation-independent mannose-6-phosphate receptor, and increases expression of constitutive photomorphogenic protein (COP)1. Expression of COP1, an E3 u2025-01-01T00:00:00Z2025 Jun2025-08-15T03:07:15.392Z2025-08-15T03:07:15.392ZS-EPMC123017404056210010.1016/j.jbc.2025.110402