title: Regulating NKX3.1 stability and function: Post-translational modifications and structural determinants.
abstract: BACKGROUND
  The androgen-regulated homeodomain transcription factor NKX3.1 plays roles in early prostate development and functions as a prostate-specific tumor suppressor. Decreased expression of NKX3.1 protein is common in primary prostate cancer. Discordance between NKX3.1 mRNA and protein levels during prostate carcinogenesis suggested a key role for post-transcriptional modifications in regulating NKX3.1 protein levels in prostate epithelial cells. Subsequent studies revealed NKX3.1 to be modified post-translationally at multiple sites.
  
  
  METHODS
  We reviewed published literature to identify and summarize post-translational modifications and structural elements critical in regulating NKX3.1 stability and levels in prostate epithelial cells.
  
  
  RESULTS
  NKX3.1 is modified post-translationally at multiple sites by different protein kinases. These modifications together with several structural determinants were identified to play an important role in NKX3.1 stability and biology.
  
  
  CONCLUSIONS
  In this review, we provide a comprehensive overview of the known post-translational modifications and structural features that impact NKX3.1. Defining factors that regulate NKX3.1 in prostate epithelial cells will extend our understanding of molecular changes that may contribute to prostate cancer initiation and progression.
authors: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut.
authors: Achuth
authors: A
authors: Padmanabhan
authors: Department of Genetics, Stanford University, Palo Alto, California.
authors: Varsha
authors: V
authors: Rao
authors: Departments of Pathology, Oncology and Urology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and the Brady Urological Research Institute at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Angelo M
authors: AM
authors: De Marzo
authors: Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, Maryland.
authors: Charles J
authors: CJ
authors: Bieberich
mesh_terms: D016147:Genes, Tumor Suppressor / Q000502:physiology; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D055550:Protein Stability; D014157:Transcription Factors / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D018398:Homeodomain Proteins; C491178:NKX3-1 protein, human; D014157:Transcription Factors
keywords: DNA damage and inflammation; phosphorylation and ubiquitination of NKX3.1; prostate cancer; protein turnover and stability; tumor suppressor