HUMAN DIPEPTIDYL-PEPTIDASE-I - GENE CHARACTERIZATION, LOCALIZATION, AND EXPRESSION

Dipeptidyl-peptidase I, a lysosomal cysteine proteinase, is important in intracellular degradation of proteins and appears to be a central c oordinator for activation of many serine proteinases in immune/inflamm atory cells, Little is known about the molecular genetics of the enzym e, In the present investigation the gene for dipeptidyl-peptidase I wa s cloned and characterized, The gene spans approximately 3.5 kilobases and consists of two exons and one intron, The genomic organization is distinct from the complex structures of the other members of the papa in-type cysteine proteinase family, By fluorescence in situ hybridizat ion, the gene was mapped to chromosomal region 11q14.1-q14.3. Analysis of the sequenced 5'-flanking region revealed no classical TATA or CCA AT box in the GC-rich region upstream of cap site, A number of possibl e regulatory elements that could account for tissue-specific expressio n were identified, Northern analyses demonstrated that the dipeptidyl- peptidase I message is expressed at high levels in lung, kidney, and p lacenta, at moderate to low levels in many organs, and at barely detec table levels in the brain, suggesting tissue-specific regulation, Amon g immune/inflammatory cells, the message is expressed at high levels i n polymorphonuclear leukocytes and alveolar macrophages and their prec ursor cells, Treatment of lymphocytes with interleukin-2 resulted in a significant increase in dipeptidyl-peptidase I mRNA levels, suggestin g that this gene is subjected to transcriptional regulation, The resul ts provide initial insights into the molecular basis for the regulatio n of human dipeptidyl-peptidase I.