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PJA1  -  praja ring finger 1, E3 ubiquitin protein...

Homo sapiens

Synonyms: E3 ubiquitin-protein ligase Praja-1, FLJ11830, PRAJA1, Praja1, RING finger protein 70, ...
 
 
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Disease relevance of PJA1

  • The alteration of ELF and/or Smad4 expression and/or function in the TGF-beta signaling pathway may be induced by enhancement of ELF degradation, which is mediated by a high-level expression of PRAJA in gastrointestinal cancers [1].
  • PRAJA is increased five-fold in human gastric cancers, and inactivates ELF [2].
 

High impact information on PJA1

  • Despite widespread inactivation of the TGF-beta pathway in gastrointestinal tumors, only a fraction of sporadic tumors exhibit inactivating mutations in early tumor formation, which suggests a role for the modulation of TGF-beta signals by stem/progenitor cell proteins, such as ELF and PRAJA [3].
  • A stable cell line that overexpresses PRAJA exhibits low levels of ELF in comparison to a Delta-PRAJA stable cell line, where ELF expression is high compared to normal controls [1].
  • In hepatocytes, half-life (t(1/2)) and rate constant for degradation (k(D)) of ELF is 1.91 h and 21.72 min(-1) when coupled with ectopic expression of PRAJA in cells stimulated by TGF-beta, compared to PRAJA-transfected unstimulated cells (t(1/2) = 4.33 h and k(D) = 9.6 min(-1)) [1].
  • Amino acid sequence analysis of the 71-kDa protein PJA1 showed 52.3% identity to human PJA2 (for praja-2, also known as NEURODAP1/KIAA0438) and also a significant identity to its homologs in rat, mouse, and zebrafish [4].
  • The alteration of ELF and/or Smad4 expression and function in the TGF-beta signaling pathway may be induced by enhancement of ELF degradation, which is mediated by the high level expression of PRAJA in gastrointestinal cancers [2].
 

Other interactions of PJA1

  • The regulation of the TGF-beta pathway through a PRAJA, a RING finger (RING-H2) protein, and ELF, a beta-Spectrin adaptor protein, both which were originally identified in endodermal stem/progenitor cells committed to foregut lineage, could play a pivotal role in gastric carcinogenesis [2].

References

  1. RING finger-dependent ubiquitination by PRAJA is dependent on TGF-beta and potentially defines the functional status of the tumor suppressor ELF. Saha, T., Vardhini, D., Tang, Y., Katuri, V., Jogunoori, W., Volpe, E.A., Haines, D., Sidawy, A., Zhou, X., Gallicano, I., Schlegel, R., Mishra, B., Mishra, L. Oncogene (2006) [Pubmed]
  2. The role of PRAJA and ELF in TGF-beta signaling and gastric cancer. Mishra, L., Katuri, V., Evans, S. Cancer Biol. Ther. (2005) [Pubmed]
  3. Adaptor proteins and ubiquinators in TGF-beta signaling. Mishra, L., Marshall, B. Cytokine Growth Factor Rev. (2006) [Pubmed]
  4. PJA1, encoding a RING-H2 finger ubiquitin ligase, is a novel human X chromosome gene abundantly expressed in brain. Yu, P., Chen, Y., Tagle, D.A., Cai, T. Genomics (2002) [Pubmed]
 
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