Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.36 (hyaluronidase)
 4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyaluronan and hyaluronidases have been proposed to be involved in tumor angiogenesis and invasion. Three hyaluronidases, HYAL1, HYAL2 and HYAL3, are located at the chromosomal region 3p21. In most small cell lung cancer (SCLC) lines the 3p21 region is part of a homozygote or heterozygote deletion. Gliomas are known to exist in a hyaluronan rich environment and express high levels of the hyaluronan receptor CD44. In a panel of SCLC and glioma cell lines the expression of HYAL1, HYAL2 and HYAL3 mRNA was examined. It was observed that the cell lines differed in their ability to splice out a retained intron in the 5' UTR of HYAL1 mRNA. A correlation seems to exist between the ability to splice out the retained 5' end intron of HYAL1 mRNA and the general hyaluronidase activity. In one cell line a substantial part of the hyaluronidase activity was abolished by immunoprecipitation of Hyal1, which strongly indicates that Hyal1 is the principal hyaluornidase in the examined cell lines. During severe hypoxia a significant reduction in both hyaluronidase mRNA and protein activity was found. These results support the theory of involvement of hyaluronidase in the angiogenic and invasive front of tumors.
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PMID:Expression and regulation patterns of hyaluronidases in small cell lung cancer and glioma lines. 1268 32

Sperm adhesion molecule1 (SPAM1), the best characterized hyaluronidase gene, is abundantly expressed in the testis. We attempted to overexpress mouse Spam1 via transgenesis using either the endogenous promoter in a BAC or a heterologous Protamine1 promoter for a Spam1 cDNA transgene. Although transgene-copy numbers ranged from 2 to 15 and transgenic transcripts were expressed, there was a general failure of overexpression of the RNA and protein in the testis of all seven founders. Also, three transgenic lines showed a modest downregulation or co-suppression of the RNA for Spam1 and Hyal5, present on the BAC. We provide evidence for the potential involvement of two co-ordinating post-transcriptional regulatory processes in the failure of overexpression: abundant endogenous antisense RNA and adenosine-uridine (AU)-rich element-mediated regulation of RNA turnover. We demonstrate that AU-rich elements (AREs) in the 3'UTR of mRNAs, well-known to interact with trans-acting proteins to target the RNA for (in)stability, are present in Spam1 RNA and specifically bind to six testicular cytoplasmic proteins. These AU-binding proteins (AUBPs) were virtually absent from the kidney where transcripts are rare, and were shown to interact with the cytoskeleton, which modulates mRNA turnover. In addition to a role in the RNAi pathway, antisense RNA can also modulate ARE-mediated regulation of mRNA by hybridizing to the AREs and specifically silencing their function. This potentially links the two processes in the regulation of Spam1 expression. We hypothesize that testicular Spam1 RNA is regulated post-transcriptionally by cis-acting ARE(s) in the 3'UTR which recognize AUBPs and which are modulated by antisense transcripts.
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PMID:Murine Spam1 mRNA: involvement of AU-rich elements in the 3'UTR and antisense RNA in its tight post-transcriptional regulation in spermatids. 1625 6