homeobox protein Nkx-3.1; homeobox protein NK-3 homolog A (NKX3-1, NKX31, NKX3A)
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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
Alternative splicing
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]
More general terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/Q99801.html
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 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: https://www.ncbi.nlm.nih.gov/pubmed/31213464
- ↑ 3.0 3.1 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: https://www.ncbi.nlm.nih.gov/pubmed/31175351