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