Disease relevance of OAZ1

• AI of the OAZ1 gene was detected in 7 of 30 informative cases of primary ovarian cancer (23%) [1].
• We have cloned the cDNA encoding the human ornithine decarboxylase antizyme from a 5'-stretch cDNA library of human B-cell lymphoma Daudi [2].
• To assess the role of the polyamine transport system in radioprotection by amifostine derivatives, human DU-145 prostate cancer cells were transfected with a cDNA that encodes antizyme (OAZ), a polyamine-inducible protein that suppresses polyamine transport under control of a minimal heat shock promoter [3].
• BACKGROUND: Gingival hyperplasia (GH) is a common side effect of cyclosporine . Azithromycin (Zithromax; AZI) is a macrolide antibiotic reported in case studies to reduce cyclosporine-induced gingival hyperplasia (CIGH) in renal transplant recipients (RTR) [4].
• The frequency of CFTR mutations was compared with that of patients with secondary obstructive azoospermia (OAZ; one out of 16, 6.3%) and non-obstructive azoospermia (NOAZ; two out of 22, 9.1%) with conserved spermatogenesis, which were similar to the general population [5].

High impact information on OAZ1

• Accumulation of PNT1A cells in the S phase progressively increased at 15, 18 and 24 h of transfection with antisense ODC and/or OAZ cDNA [6].
• Ornithine decarboxylase antizyme 1 and 2 (OAZ1 and OAZ2) are expressed ubiquitously, and control the intracellular concentration of polyamines [7].
• In contrast, the mRNA level of somatic ornithine decarboxylase antizyme 1 (OAZ1) decreased markedly at the late stages of haploid germ cell differentiation [8].
• Assignment of the human antizyme gene (OAZ) to chromosome 19p13.3 by fluorescence in situ hybridization [9].
• Our results directly demonstrate that downregulation of AZI regulates ODC activity, intracellular polyamine levels, and cell growth through regulating antizyme activity [10].

Biological context of OAZ1

• Moreover, silencing AZI expression decreased intracellular polyamine levels, reduced cell proliferation, and prolonged population doubling time [10].
• A commonly deleted region in ovarian cancer on chromosome 19p13.3, not including the OAZ1 gene [1].
• These results suggest that one or more tumor suppressor genes other than OAZ1 exist near the D19S216 locus on 19p13.3 [1].
• Subsequent multiplex fluorescent microsatellite analysis at 7 loci on 19p and at 4 loci on 19q in 50 primary ovarian tumors revealed a commonly deleted region, approximately 4.7 Mb, between the D19S424 and D19S884 loci on 19p13.3 in the vicinity of the OAZ1 locus [1].
• The gene for antizyme (OAZ1) is mapped to 19p13.3, where frequent allelic imbalance (AI) is observed in ovarian cancer [1].

Anatomical context of OAZ1

• Mutations of the OAZ1 gene, including the entire coding region and associated promoter region, were examined in 50 primary ovarian tumors and 8 ovarian cancer cell lines by PCR-SSCP and sequencing analyses [1].
• We report the cloning of a cDNA encoding the human homolog of ornithine decarboxylase antizyme from a human gingival fibroblast cDNA library [11].

Associations of OAZ1 with chemical compounds

• The antizyme-induced growth inhibition could be reversed by addition of putrescine or by the co-expression of AZI [12].
• In a previous study, we demonstrated that oligoasthenozoospermic (OAZ) patients had two types of testosterone response to human chorionic gonadotrophin (HCG) administration: group 1 (OAZ-1) had an altered, monophasic (no first peak) response, and group 2 (OAZ-2) had a normal biphasic response [13].
• This antiproliferative action was not due to an effect on ornithine decarboxylase antizyme, since its intracellular concentration was not significantly changed by agmatine [14].

Physical interactions of OAZ1

• In the present study, we show by yeast two- and three-hybrid protein-protein interaction studies that AZI interacts with all members of the antizyme family and is capable of disrupting the interaction between each antizyme and ODC [12].

Other interactions of OAZ1

• ODC-p might also function as a brain- and testis-specific AZI [15].
• This study also suggests that highly expressed AZI may be partly responsible for increased ODC activity and cellular transformation [10].
• Antizyme 1 has been shown to be negatively regulated through the AZI (antizyme inhibitor) that binds antizyme 1 with higher affinity compared with ODC [12].
• Smad1 forms a complex with a proteasome beta subunit HsN3 and the ornithine decarboxylase antizyme (Az) [16].

Analytical, diagnostic and therapeutic context of OAZ1

• The protein interactions could be confirmed by immunoprecipitation of the human ODC-antizyme 2-AZI complexes [12].
• Molecular cloning and sequencing of a human cDNA encoding ornithine decarboxylase antizyme [11].

References