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homeobox protein Nkx-3.1; homeobox protein NK-3 homolog A (NKX3-1, NKX31, NKX3A)

Function: - transcription factor - binds preferentially the consensus sequence 5'-TAAGT[AG]-3' - transcriptional repressor, growth suppressor, mediator of apoptosis, inducer of antioxidants, & enhancer of DNA repair [2] - play a role in normal prostate development, regulating proliferation of glandular epithelium & in the formation of ducts in prostate - acts as a tumor suppressor controlling prostate carcinogenesis - inhibits proliferation & invasion activities of PC-3 prostate cancer cells - ubiquitinated by TOPORS; monoubiquitinated at several residues & also polyubiquitinated on single residues - steady state turnover of NKX3.1 is mediated by DYRK1B phosphorylation at NKX3.1 Ser-185 that leads to polyubiquitination & proteasomal degradation [2] - PTEN is an NKX3.1 phosphatase that protects NKX3.1 from degradation [2] - interacts with serum response factor (SRF) - interacts with SPDEF - interacts with WDR77 - interacts with TOPORS which polyubiquitinates NKX3-1 & induces its proteasomal degradation Structure: - belongs to the NK-3 homeobox family - contains 1 homeobox DNA-binding domain Compartment: nucleus Alternative splicing: - named isoforms=5 - additional isoforms seem to exist Expression: - highly expressed in the prostate - expressed, at a lower level, in testis - expression is induced by androgens &, in the LNCAP cell line, by estrogens Pathology: - NKX3.1 is the most commonly deleted gene in prostate cancer [2] - ubiquitous tumor suppressor that is often decreased in prostate cancer during tumor progression [2] - androgenic control may be lost in prostate cancer cells during tumor progression from an androgen-dependent to an androgen-independent phase Laboratory: - NKX3.1 immunostaining on fine needle aspirations smears detects metastatic prostatic carcinoma of conventional & ductal types, but not small cell carcinoma [3]

General

homeobox protein

Properties

SIZE: entity length = 234 aa MW = 26 kD COMPARTMENT: cell nucleus MOTIF: homeodomain SITE: 124-183

Database Correlations

OMIM 602041 UniProt Q99801 Pfam PF00046 Entrez Gene 4824 Kegg hsa:4824

References

  1. UniProt :accession Q99801
  2. Bowen C, Ostrowski MC, Leone G, Gelmann EP. Loss of PTEN Accelerates NKX3.1 Degradation to Promote Prostate Cancer Progression. Cancer Res. 2019 Jun 18. pii: canres.4110.2018. PMID: 31213464
  3. Gan Q, Joseph CT, Guo M, Zhang M, Sun X, Gong Y. Utility of NKX3.1 Immunostaining in the Detection of Metastatic Prostatic Carcinoma on Fine-Needle Aspiration Smears. Am J Clin Pathol. 2019 Jun 8. PMID: 31175351