Human Dipeptidyl-peptidase I

Dipeptidyl-peptidase I, a lysosomal cysteine proteinase, is important in intracellular degradation of proteins and appears to be a central coordinator for activation of many serine proteinases in immune/inflammatory cells. Little is known about the molecular genetics of the enzyme. In the present investigation the gene for dipeptidyl-peptidase I was 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 papain-type cysteine proteinase family. By fluorescence in situ hybridization, the gene was mapped to chromosomal region 11q14.1-q14.3. Analysis of the sequenced 5′-flanking region revealed no classical TATA or CCAAT box in the GC-rich region upstream of cap site. A number of possible regulatory elements that could account for tissue-specific expression were identified. Northern analyses demonstrated that the dipeptidyl-peptidase I message is expressed at high levels in lung, kidney, and placenta, at moderate to low levels in many organs, and at barely detectable levels in the brain, suggesting tissue-specific regulation. Among immune/inflammatory cells, the message is expressed at high levels in polymorphonuclear leukocytes and alveolar macrophages and their precursor cells. Treatment of lymphocytes with interleukin-2 resulted in a significant increase in dipeptidyl-peptidase I mRNA levels, suggesting that this gene is subjected to transcriptional regulation. The results provide initial insights into the molecular basis for the regulation of human dipeptidyl-peptidase I.

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