Profound Impact of Decline in N-Acetylgalactosamine-4-Sulfatase (Arylsulfatase B) on Molecular Pathophysiology and Human Diseases
The enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB) was originally identified as a lysosomal enzyme which was deficient in Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy Syndrome). The newly directed attention to the impact of ARSB in human pathobiology indicates a broader, more p...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/21/13146 |
| _version_ | 1797467935026970624 |
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| author | Joanne K. Tobacman Sumit Bhattacharyya |
| author_facet | Joanne K. Tobacman Sumit Bhattacharyya |
| author_sort | Joanne K. Tobacman |
| collection | DOAJ |
| description | The enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB) was originally identified as a lysosomal enzyme which was deficient in Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy Syndrome). The newly directed attention to the impact of ARSB in human pathobiology indicates a broader, more pervasive effect, encompassing roles as a tumor suppressor, transcriptional mediator, redox switch, and regulator of intracellular and extracellular-cell signaling. By controlling the degradation of chondroitin 4-sulfate and dermatan sulfate by removal or failure to remove the 4-sulfate residue at the non-reducing end of the sulfated glycosaminoglycan chain, ARSB modifies the binding or release of critical molecules into the cell milieu. These molecules, such as galectin-3 and SHP-2, in turn, influence crucial cellular processes and events which determine cell fate. Identification of ARSB at the cell membrane and in the nucleus expands perception of the potential impact of decline in ARSB activity. The regulation of availability of sulfate from chondroitin 4-sulfate and dermatan sulfate may also affect sulfate assimilation and production of vital molecules, including glutathione and cysteine. Increased attention to ARSB in mammalian cells may help to integrate and deepen our understanding of diverse biological phenomenon and to approach human diseases with new insights. |
| first_indexed | 2024-03-09T19:00:51Z |
| format | Article |
| id | doaj.art-a727909c4e3842bab628766b1afa7f70 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T19:00:51Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a727909c4e3842bab628766b1afa7f702023-11-24T05:03:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123211314610.3390/ijms232113146Profound Impact of Decline in N-Acetylgalactosamine-4-Sulfatase (Arylsulfatase B) on Molecular Pathophysiology and Human DiseasesJoanne K. Tobacman0Sumit Bhattacharyya1Jesse Brown VA Medical Center, University of Illinois at Chicago, Chicago, IL 60612, USAJesse Brown VA Medical Center, University of Illinois at Chicago, Chicago, IL 60612, USAThe enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB) was originally identified as a lysosomal enzyme which was deficient in Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy Syndrome). The newly directed attention to the impact of ARSB in human pathobiology indicates a broader, more pervasive effect, encompassing roles as a tumor suppressor, transcriptional mediator, redox switch, and regulator of intracellular and extracellular-cell signaling. By controlling the degradation of chondroitin 4-sulfate and dermatan sulfate by removal or failure to remove the 4-sulfate residue at the non-reducing end of the sulfated glycosaminoglycan chain, ARSB modifies the binding or release of critical molecules into the cell milieu. These molecules, such as galectin-3 and SHP-2, in turn, influence crucial cellular processes and events which determine cell fate. Identification of ARSB at the cell membrane and in the nucleus expands perception of the potential impact of decline in ARSB activity. The regulation of availability of sulfate from chondroitin 4-sulfate and dermatan sulfate may also affect sulfate assimilation and production of vital molecules, including glutathione and cysteine. Increased attention to ARSB in mammalian cells may help to integrate and deepen our understanding of diverse biological phenomenon and to approach human diseases with new insights.https://www.mdpi.com/1422-0067/23/21/13146N-acetylgalactosamine-4-sulfataseArylsulfatase Bchondroitin 4-sulfatedermatan sulfatesulfated glycosaminoglycansmucopolysaccharidosis |
| spellingShingle | Joanne K. Tobacman Sumit Bhattacharyya Profound Impact of Decline in N-Acetylgalactosamine-4-Sulfatase (Arylsulfatase B) on Molecular Pathophysiology and Human Diseases International Journal of Molecular Sciences N-acetylgalactosamine-4-sulfatase Arylsulfatase B chondroitin 4-sulfate dermatan sulfate sulfated glycosaminoglycans mucopolysaccharidosis |
| title | Profound Impact of Decline in N-Acetylgalactosamine-4-Sulfatase (Arylsulfatase B) on Molecular Pathophysiology and Human Diseases |
| title_full | Profound Impact of Decline in N-Acetylgalactosamine-4-Sulfatase (Arylsulfatase B) on Molecular Pathophysiology and Human Diseases |
| title_fullStr | Profound Impact of Decline in N-Acetylgalactosamine-4-Sulfatase (Arylsulfatase B) on Molecular Pathophysiology and Human Diseases |
| title_full_unstemmed | Profound Impact of Decline in N-Acetylgalactosamine-4-Sulfatase (Arylsulfatase B) on Molecular Pathophysiology and Human Diseases |
| title_short | Profound Impact of Decline in N-Acetylgalactosamine-4-Sulfatase (Arylsulfatase B) on Molecular Pathophysiology and Human Diseases |
| title_sort | profound impact of decline in n acetylgalactosamine 4 sulfatase arylsulfatase b on molecular pathophysiology and human diseases |
| topic | N-acetylgalactosamine-4-sulfatase Arylsulfatase B chondroitin 4-sulfate dermatan sulfate sulfated glycosaminoglycans mucopolysaccharidosis |
| url | https://www.mdpi.com/1422-0067/23/21/13146 |
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