Disease relevance of HYAL1

• Mutations in HYAL1, a member of a tandemly distributed multigene family encoding disparate hyaluronidase activities, cause a newly described lysosomal disorder, mucopolysaccharidosis IX [1].
• Using bladder tissues and cells, prostate cancer cells, and kidney tissues and performing reverse transcription-PCR, cDNA cloning, DNA sequencing, and in vitro translation, we identified splice variants of HYAL1 and HYAL3 [2].
• OBJECTIVE: The extracellular glycosaminoglycan hyaluronan (HA) and its degradative enzymes, hyaluronidases (Hyal), play important roles in tumor metastasis and angiogenesis [3].
• Real-time RT-PCR was used to determine the mRNA expression of Hyal 1, Hyal 2 (n = 13) and Hyal 3 (n = 11) in endometrial carcinomas [3].
• In ten well-established breast cancer cell lines, the expression of the genes for each hyaluronan synthase (HAS) and hyaluronidase (Hyal) isoform was quantitated using real-time and reverse transcriptase polymerase chain reaction (PCR) [4].

High impact information on HYAL1

• The discovery of Ca(2+) transport by mitochondria is conventionally credited to De Luca and Engstrom, and Vasington and Murphy, who showed in 1961-1962 that Ca(2+) was taken up by isolated mitochondria using respiratory or ATP energy [5].
• The evolution of the enzymatic systems for (i) DNA replication; and (ii) membrane and cell wall biosynthesis, enabled independent escape of the first archaebacterial and eubacterial cells from their hydrothermal hatchery, within which the LUCA itself remained confined [6].
• Furthermore, we could not detect hyaluronidase activity associated with or secreted by cells expressing HYAL2, whereas we could easily detect such activity from cells expressing the related serum hyaluronidase HYAL1 [7].
• These genes, HYAL1 and HYAL2, encode two distinct lysosomal hyaluronidases with different substrate specificities [1].
• We identified two mutations in the HYAL1 alleles of the patient, a 1412G --> A mutation that introduces a nonconservative amino acid substitution (Glu268Lys) in a putative active site residue and a complex intragenic rearrangement, 1361del37ins14, that results in a premature termination codon [1].

Chemical compound and disease context of HYAL1

• Evaluation of the prognostic potential of hyaluronic acid and hyaluronidase (HYAL1) for prostate cancer [8].

Biological context of HYAL1

• The Hyal-1 gene, HYAL1, also known as LUCA-1, maps to chromosome 3p21.3 within a candidate tumor suppressor gene locus defined by homozygous deletions and by functional tumor suppressor activity [9].
• The hyaluronidase gene HYAL1 maps to chromosome 3p21.2-p21.3 in human and 9F1-F2 in mouse, a conserved candidate tumor suppressor locus [10].
• The HYAL1 mRNA sequence was used in a homology search of the mouse database of expressed sequence tags (dbEST) [10].
• Sequence-tagged sites derived from the HYAL1 gene from both species were used to isolate P1 genomic clones that were used as probes for fluorescence in situ hybridization [10].
• The Hyal genes were all found to have four exons, and exons 2-4 exhibited the highest sequence conservation [11].

Anatomical context of HYAL1

• Comparative genomic and fluorescence in situ hybridization identified chromosomal deletions of one allele of HYAL1 in six of seven cell lines [9].
• RESULTS: PDL fibroblasts expressed HYAL1 and HYAL2 mRNAs, but not PH-20 mRNA [12].
• In the univariate analysis, preoperative PSA, Gleason sum, stage, margin, seminal vesicle, extra-prostatic extension (EPE), HA, HYAL1, and HA-HYAL1 were significant in predicting progression (P < 0.05) [8].
• Whereas vector and moderate HYAL1 producers generated muscle and blood vessel infiltrating tumors, HYAL1-AS tumors were benign and contained smaller capillaries [13].
• A tumor cell line was constructed with an ecdysone-inducible promoter located upstream from the cDNA of HYAL1 [14].

Associations of HYAL1 with chemical compounds

• Expression of tumor markers hyaluronic acid and hyaluronidase (HYAL1) in head and neck tumors [15].
• Since individuals react to different degrees to HMW, HYAL, and PHOS A, there does not appear to be a single principal allergen in honeybee venom [16].
• We have previously shown that maximal Ret-P-Man synthesis occurs in vitro at 20-30 min, followed by a subsequent loss of mannose from Ret-P-Man, suggestive of an intermediary function of Ret-P-Man and/or Ret-P-Man breakdown [Shidoji, Silverman-Jones & De Luca (1982) Biochem. J [17].
• The presence, but not the number, of sulfate groups on the sHA molecule determined its potency (e.g., IC50 for HYAL-1: sHA2.0, 0.019 microM; sHA2.75, 0.0083 microM) [18].
• Histamine release in response to ACID P appears harder to block with hyperimmune beekeeper plasma than that provoked by PLA2 or HYAL (p less than 0.01) [19].

Regulatory relationships of HYAL1

• The expression of HYAL1 mRNA was enhanced by about 3.5- and 3.7-fold at maximum after 1-hour stimulation with 1 ng/ml IL-1beta and after 3-hour stimulation with 10 ng/ml TNF-alpha, respectively [12].

Other interactions of HYAL1

• Analogously to PH-20, the smaller isozyme of HYAL1 is likely to be a proteolytically processed product of the larger isozyme [20].
• In contrast to BMP-7, IL-1beta did not influence Hyal expression [21].
• Hyaluronan synthase (HAS) or hyaluronidase (HYAL) mRNA levels were assessed by reverse transcription-PCR [22].
• Coexpression of Hyal1 with HAS2 diminished HA retention but restored growth kinetics, supporting a possible combined role for excess HA synthesis and processing in maximizing unrestricted growth of prostate cancer cells [23].

Analytical, diagnostic and therapeutic context of HYAL1

• Initial RT - PCR analyses demonstrated marked discrepancies between levels of HYAL1 mRNA and protein [9].
• 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 [24].
• Immunoblotting revealed more HYAL 1 and 2 in the myofibroblast conditioned medium [22].
• We evaluated the prognostic potential of HA and HYAL1 in CaP by immunohistochemistry [8].
• Reverse transcription-polymerase chain reaction, cloning, and sequence analyses revealed the expression of an HYAL1 transcript in bladder cancer lines [25].

References