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Critical Reviews in Oral Biology & Medicine
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13(6):485-508 (2002)     Crit Rev Oral Biol Med
© 2002 International and American Associations for Dental Research

SALIVARY (SD-TYPE) CYSTATINS: OVER ONE BILLION YEARS IN THE MAKING—BUT TO WHAT PURPOSE?

D.P. Dickinson

Medical College of Georgia, School of Dentistry, Department of Oral Biology and Maxillofacial Pathology, 1120 15th Street, Augusta, GA 30912; ddickins{at}mail.mcg.edu

Human saliva contains relatively abundant proteins that are related ancestrally in sequence to the cystatin superfamily. Most, although not all, members of this superfamily are potent inhibitors of cysteine peptidases. Four related genes have been identified, CST1, 2, 4 and 5, encoding cystatins SN, SA, S, and D, respectively. CST1, 4, and probably CST5 are now known to be expressed in a limited number of other tissues in the body, primarily in exocrine epithelia, and the term SD-type cystatin is more appropriate than ’salivary cystatin’. These genes are co-ordinately regulated in the submandibular gland during post-natal development. The organization of these tissue-specifically-expressed genes in the genome, and their phylogeny, indicate that they evolved from an ancestral housekeeping gene encoding the ubiquitously expressed cystatin C, and are members of a larger protein family. Their relationship to rat cystatin S, a developmentally regulated rodent submandibular gland protein, remains to be established. In this review, the evolution of the SD-type cystatins in the cystatin superfamily, their genomics, expression, and structure-function relationships are examined and compared with known cystatin functions, with the goal of providing clues to their biological roles.

Key Words: Cystatin • cysteine protease • superfamily • evolution • saliva • human • function

Critical Reviews in Oral Biology & Medicine, Vol. 13, No. 6, 485-508 (2002)
DOI: 10.1177/154411130201300606


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