RGD Reference Report - Cloning of a novel retinoid-inducible serine carboxypeptidase from vascular smooth muscle cells. - Rat Genome Database

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Cloning of a novel retinoid-inducible serine carboxypeptidase from vascular smooth muscle cells.

Authors: Chen, J  Streb, JW  Maltby, KM  Kitchen, CM  Miano, JM 
Citation: Chen J, etal., J Biol Chem 2001 Sep 7;276(36):34175-81.
RGD ID: 70518
Pubmed: PMID:11447226   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M104162200   (Journal Full-text)

Retinoids block smooth muscle cell (SMC) proliferation and attenuate neointimal formation after vascular injury, presumably through retinoid receptor-mediated changes in gene expression. To identify target genes in SMC whose encoded proteins could contribute to such favorable biological effects, we performed a subtractive screen for retinoid-inducible genes in cultured SMC. Here, we report on the cloning and initial characterization of a novel retinoid-inducible serine carboxypeptidase (RISC). Expression of RISC is low in cultured SMC but progressively increases over a 5-day time-course treatment with all-trans-retinoic acid. A near full-length rat RISC cDNA was cloned and found to have a 452-amino acid open reading frame containing an amino-terminal signal sequence, followed by several conserved domains comprising the catalytic triad common to members of the serine carboxypeptidase family. In vitro transcription and translation experiments showed that the rat RISC cDNA generates an approximately 51-kDa protein. Confocal immunofluorescence microscopy of COS-7 cells transiently transfected with a RISC-His tag plasmid revealed cytosolic localization of the fusion protein. Western blotting studies using conditioned medium from transfected COS-7 cells suggest that RISC is a secreted protein. Tissue Northern blotting studies demonstrated robust expression of RISC in rat aorta, bladder, and kidney with much lower levels in all other tissues analyzed; high level RISC expression was also observed in human kidney. In situ hybridization verified the localization of RISC to medial SMC of the adult rat aorta. Interestingly, expression in kidney was restricted to proximal convoluted tubules; little or no expression was observed in glomerular cells, distal convoluted and collecting tubules, or medullary cells. Radiation hybrid mapping studies placed the rat RISC locus on chromosome 10q. These studies reveal a novel retinoid-inducible protease whose activity may be involved in vascular wall and kidney homeostasis.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
retinoic acid metabolic process  IEP 70518 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
serine-type carboxypeptidase activity  TAS 70518 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Scpep1  (serine carboxypeptidase 1)

Objects referenced in this article
Gene SCPEP1 serine carboxypeptidase 1 Homo sapiens
Gene Scpep1 serine carboxypeptidase 1 Mus musculus

Additional Information