Affinage

OAZ2

Ornithine decarboxylase antizyme 2 · UniProt O95190

Length
189 aa
Mass
21.0 kDa
Annotated
2026-04-29
21 papers in source corpus 5 papers cited in narrative 5 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

OAZ2 is an ornithine decarboxylase (ODC) antizyme that negatively regulates intracellular polyamine concentrations by binding to and inactivating ODC in a polyamine-dependent feedback loop (PMID:19893612). OAZ2 participates in a ubiquitin-independent proteasomal degradation pathway that targets c-Myc; RNA-edited AZIN1 delays this OAZ2-mediated c-Myc degradation, leading to increased IL-8 secretion and tumor angiogenesis (PMID:35365616). OAZ2 mRNA stability is directly regulated by miR-34a through its 3′UTR, and loss of this miR-34a/OAZ2 axis enhances ABC transporter activation and multidrug resistance in colon cancer cells (PMID:30175154).

Mechanistic history

Synthesis pass · year-by-year structured walk · 3 steps
  1. 2009 Medium

    Establishing OAZ2 as a ubiquitously expressed ODC antizyme resolved its basic biochemical identity: OAZ2 binds and inactivates ODC to control intracellular polyamine levels in a feedback manner, distinguishing it from the germline-specific OAZ3.

    Evidence OAZ3 knockout mouse model with polyamine measurements and comparative expression analysis across tissues

    PMID:19893612

    Open questions at the time
    • Non-redundant functions of OAZ2 versus OAZ1 remain undefined
    • No OAZ2-specific knockout phenotype reported
    • Tissue-specific quantitative contribution of OAZ2 to polyamine homeostasis not dissected
  2. 2018 Medium

    Identifying miR-34a as a direct positive regulator of OAZ2 mRNA stability revealed a post-transcriptional control layer and connected OAZ2 loss to chemoresistance through ABC transporter activation.

    Evidence Luciferase reporter assays on OAZ2 3′UTR, miR-34a overexpression/inhibition with drug-response assays in colon cancer cells and clinical histoculture samples

    PMID:30175154

    Open questions at the time
    • Mechanism by which miR-34a stabilizes rather than represses OAZ2 mRNA is unconventional and not mechanistically resolved
    • Whether OAZ2 protein levels change proportionally to mRNA was not directly demonstrated
    • Single-lab finding without independent replication
  3. 2022 Medium

    Demonstrating that RNA-edited AZIN1 delays c-Myc degradation through an OAZ2-dependent ubiquitin-independent proteasome pathway expanded OAZ2's role beyond ODC regulation to include control of oncoprotein stability and downstream angiogenesis via IL-8.

    Evidence In vitro and in vivo experiments with edited AZIN1 constructs, pathway analysis linking OAZ2 to ubiquitin-independent proteasomal degradation of c-Myc

    PMID:35365616

    Open questions at the time
    • Direct physical interaction between OAZ2 and c-Myc has not been demonstrated
    • Whether OAZ2 acts as a direct adaptor for proteasomal targeting of c-Myc or acts indirectly remains unclear
    • Limited orthogonal validation of OAZ2-specific contribution

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the non-redundant in vivo functions of OAZ2 versus OAZ1, the structural basis for OAZ2-mediated ubiquitin-independent proteasomal targeting, and whether OAZ2 directly binds substrates beyond ODC.
  • No OAZ2-specific genetic loss-of-function model exists
  • No structural data for OAZ2 or OAZ2–substrate complexes reported
  • Full substrate repertoire of OAZ2 in ubiquitin-independent degradation unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 2
Localization
GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 2
Partners
AZIN1ODC1

Evidence

Reading pass · 5 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2022 RNA-edited AZIN1 promotes tumor angiogenesis via an OAZ2-mediated ubiquitin-independent proteasome pathway that delays c-Myc degradation, leading to increased IL-8 mRNA levels and secretion of the angiogenic factor IL-8. In vitro and in vivo experiments with RNA-edited AZIN1 constructs, combined with pathway analysis linking OAZ2 to ubiquitin-independent proteasomal degradation of c-Myc Cell death & disease Medium 35365616
2018 miR-34a directly targets the 3'UTR of OAZ2 mRNA to positively regulate its mRNA stability, and suppression of this miR-34a/OAZ2 signaling axis by chemotherapeutic agents enhances ABC transporter activation and antiapoptosis pathways, contributing to multidrug resistance in colon cancer cells. Luciferase reporter assays targeting OAZ2 3'UTR, ectopic miR-34a expression/inhibition with drug-response assays, and histoculture drug response assay in clinical samples Journal of immunology research Medium 30175154
2009 OAZ1 and OAZ2 are expressed ubiquitously and control intracellular polyamine concentrations in a feedback manner by binding to and inactivating ornithine decarboxylase (ODC), whereas OAZ3 is expressed specifically in germline cells during spermiogenesis. Genetic knockout mouse model (OAZ3 knockout), polyamine concentration measurements, and expression analysis PLoS genetics Medium 19893612
2011 Increased H3K4me3 histone modification at the OAZ1 promoter (but not specifically OAZ2 promoter) is associated with upregulation of OAZ1 and OAZ2 expression in the prefrontal cortex of suicide completers, implicating epigenetic regulation of OAZ2 expression via open chromatin marks. Chromatin immunoprecipitation (ChIP) for H3K4me3 at promoter regions, correlation with gene expression in human postmortem brain tissue The international journal of neuropsychopharmacology Low 22008221
2021 UXT knockdown in colorectal cancer cells increases expression of OAZ1, OAZ2, and OAZ3 (which negatively regulate polyamine synthesis) and decreases putrescine levels, while UXT overexpression has the opposite effect, placing OAZ2 downstream of UXT in polyamine metabolic regulation. siRNA knockdown and overexpression of UXT with measurement of OAZ1/2/3 mRNA and putrescine levels; in vivo xenograft tumor model Human cell Low 41931169

Source papers

Stage 0 corpus · 21 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 ODC1 is a critical determinant of MYCN oncogenesis and a therapeutic target in neuroblastoma. Cancer research 218 19047152
2009 OAZ-t/OAZ3 is essential for rigid connection of sperm tails to heads in mouse. PLoS genetics 86 19893612
2010 The polyamine metabolism genes ornithine decarboxylase and antizyme 2 predict aggressive behavior in neuroblastomas with and without MYCN amplification. International journal of cancer 56 19960435
2011 Effects of histone modifications on increased expression of polyamine biosynthetic genes in suicide. The international journal of neuropsychopharmacology 39 22008221
2022 A novel mechanism for A-to-I RNA-edited AZIN1 in promoting tumor angiogenesis in colorectal cancer. Cell death & disease 33 35365616
2012 Effects of promoter methylation on increased expression of polyamine biosynthetic genes in suicide. Journal of psychiatric research 32 23260169
2018 miR-34a Regulates Multidrug Resistance via Positively Modulating OAZ2 Signaling in Colon Cancer Cells. Journal of immunology research 31 30175154
2011 Ornithine decarboxylase antizyme Oaz3 modulates protein phosphatase activity. The Journal of biological chemistry 24 21712390
2010 Clock genes and their genomic distributions in three species of salmonid fishes: Associations with genes regulating sexual maturation and cell cycling. BMC research notes 23 20670436
2017 Effect of Oaz1 overexpression on goose ovarian granulosa cells. Amino acids 18 28324173
2014 Gene polymorphisms in the ornithine decarboxylase-polyamine pathway modify gastric cancer risk by interaction with isoflavone concentrations. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 18 25079701
2020 Deep Transcriptomic Analysis Reveals the Dynamic Developmental Progression during Early Development of Channel Catfish (Ictalurus punctatus). International journal of molecular sciences 12 32748829
2002 Structure and promoter activity of the gene encoding ornithine decarboxylase antizyme expressed exclusively in haploid germ cells in testis (OAZt/Oaz3). Gene 12 12426106
2016 Effects of agmatine on secretion of interferon tau and catecholamines and expression of genes related to production of polyamines by ovine trophectoderm cells. Amino acids 11 27074718
2021 Gene Banks as Reservoirs to Detect Recent Selection: The Example of the Asturiana de los Valles Bovine Breed. Frontiers in genetics 8 33633776
2014 Molecular cloning and mRNA expression analysis of ornithine decarboxylase antizyme 2 in ovarian follicles of the Sichuan white goose (Anser cygnoides). Gene 6 24831833
2022 Identifying transcript-level differential expression in primary human immune cells. Molecular immunology 5 36527757
2021 Exogenous spermidine affects polyamine metabolism in the mouse hypothalamus. Open life sciences 4 33817296
2024 Whole-genome analysis of resilience based on the stability of reproduction performance during a porcine reproductive and respiratory syndrome virus outbreak in sows. Animal : an international journal of animal bioscience 2 39226776
2026 Ubiquitously expressed prefoldin-like chaperone (UXT) regulates putrescine metabolism and promotes colorectal cancer progression. Human cell 0 41931169
2025 Development of a Diagnostic Model for Focal Segmental Glomerulosclerosis: Integrating Machine Learning on Activated Pathways and Clinical Validation. International journal of general medicine 0 40026806