Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cystatin M/E is a high affinity inhibitor of the asparaginyl endopeptidase legumain, and we have previously reported that both proteins are likely to be involved in the regulation of stratum corneum formation in skin. Although cystatin M/E contains a predicted binding site for papain-like cysteine proteases, no high affinity binding for any member of this family has been demonstrated so far. We report that human cathepsin V (CTSV) and human cathepsin L (CTSL) are strongly inhibited by human cystatin M/E. Kinetic studies show that Ki values of cystatin M/E for the interaction with CTSV and CTSL are 0.47 and 1.78 nM, respectively. On the basis of the analogous sites in cystatin C, we used site-directed mutagenesis to identify the binding sites of these proteases in cystatin M/E. We found that the W135A mutant was rendered inactive against CTSV and CTSL but retained legumain-inhibiting activity. Conversely, the N64A mutant lost legumain-inhibiting activity but remained active against the papain-like cysteine proteases. We conclude that legumain and papain-like cysteine proteases are inhibited by two distinct non-overlapping sites. Using immunohistochemistry on normal human skin, we found that cystatin M/E co-localizes with CTSV and CTSL. In addition, we show that CTSL is the elusive enzyme that processes and activates epidermal transglutaminase 3. The identification of CTSV and CTSL as novel targets for cystatin M/E, their (co)-expression in the stratum granulosum of human skin, and the activity of CTSL toward transglutaminase 3 strongly imply an important role for these enzymes in the differentiation process of human epidermis.
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PMID:Cystatin M/E is a high affinity inhibitor of cathepsin V and cathepsin L by a reactive site that is distinct from the legumain-binding site. A novel clue for the role of cystatin M/E in epidermal cornification. 1656 75

Immature spermatozoa undergo series of events in the epididymis to acquire motility and fertilizing ability. These events are a direct result of exposure to, and interaction with, the luminal environment created by the epididymal epithelium. The three conventional regions of the epididymis namely; caput, corpus and cauda have been identified to play specific roles in the epididymal maturation process of the spermatozoa; their respective roles have been associated with specific gene expression patterns that account for the composition of the luminal fluid that bathe the spermatozoa as they transit through the epididymal lumen and ensure their maturation. The identification of genes expressed in a region-specific manner provides valuable insight into the functional differences among the regions. Microarray technology has previously been employed in region-specific gene expression studies using the epididymis as a model in different species such as mouse, rat, boar and human. However, to characterize gene expression in the different regions of the epididymis, RNA-seq analysis was used in our study to examine gene expressions in the caput, corpus, and cauda of yak epididymis. Comparative transcriptomic analysis was performed between region pairs in the order; caput vs corpus, caput vs cauda and corpus vs cauda. DEGs among the various region pairs were detected and functional analysis were performed for the detected DEGs. Overall, the caput vs cauda epididymidis pair produced the highest number of DEGs (49.4%) while the corpus vs cauda pair produced the least number of DEGs (19.3%). The caput segment demonstrated relatively high expression of Sal1, LCN6, PTDS, DEFB109, DEFB 119, DEFB 123, SPAG11, PROC, CST3, ADAM28, KCNJ12 and SLC13A2; corpus epididymis demonstrated relatively high expression of MAN2B2, ELP, ZFYVE21, GLB1L, BMP4, DEFB125, PPP1R10, RIOX2, TKDP1, DEFB106A, NPBWR1 and SLC28A1; and the cauda epididymis, demonstrated relatively high expressions of MCT7, PAG4, OAS1, TGM3 and PRSS45. Gene Ontology results showed that DEGs in the caput vs corpus and corpus vs cauda pairs were mostly enriched in the cell/cell part GO term. On the other hand, DEGs in the caput vs cauda pair was were mostly enriched in the cellular process term. KEGG pathway annotation was also performed for DEGs among the various groups. AMPK signaling pathway, which is characterized by the ratio between cellular AMP and ATP and also determines cellular energy state, was selected from among the top five KEGG pathways for DEGs in the caput vs corpus pair. Our results showed that some down-regulated DEGs in the caput and corpus pair such as HN4a, eEF2K and CFTR were present and played significant roles in the AMPK signaling pathway. In the corpus vs cauda pair, our results showed that up-regulated DEGs such as XDH, TRMP2 and ENTPD were involved in the purine metabolism KEGG pathway, which was among top five KEGG pathways for DEGs in this pair. Pentose phosphate pathway functions in antioxidation to protect both the spermatozoa and epididymis from oxidative damage; it was among top five KEGG pathways for DEGs in the caput vs cauda pair. Our results also showed that down-regulated genes in the caput vs cauda pair such as TALDO1 was found to be involved in the Pentose phosphate pathway. The significance of the upregulated and downregulated genes on the pathways were elucidated. SAL1, which showed high expression in the caput, had previously not been demonstrated in the epididymis, needs further investigation to establish its unique role in the yak epididymis.
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PMID:Region-specific gene expression in the epididymis of Yak. 3140 23