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Protein TMEPAI

Definition:

Functions as a negative regulator of TGF-beta signaling and thereby probably plays a role in cell proliferation, differentiation, apoptosis, motility, extracellular matrix production and immunosuppression. In the canonical TGF-beta pathway, ZFYVE9/SARA recruits the intracellular signal transducer and transcriptional modulators SMAD2 and SMAD3 to the TGF-beta receptor. Phosphorylated by the receptor, SMAD2 and SMAD3 then form a heteromeric complex with SMAD4 that translocates to the nucleus to regulate transcription. Through interaction with SMAD2 and SMAD3, LDLRAD4 may compete with ZFYVE9 and SMAD4 and prevent propagation of the intracellular signal. Also involved in down-regulation of the androgen receptor (AR), enhancing ubiquitination and proteasome-mediated degradation of AR, probably by recruiting NEDD4.

References:

[1]. Naoko Nakano, et al. C18 ORF1, a novel negative regulator of transforming growth factor-β signaling. J Biol Chem. 2014 May 2;289(18):12680-92. [Content Brief]

[2]. Hongyun Li, et al. A feedback loop between the androgen receptor and a NEDD4-binding protein, PMEPA1, in prostate cancer cells. J Biol Chem. 2008 Oct 24;283(43):28988-95. [Content Brief]

[3]. Yukihide Watanabe, et al. TMEPAI, a transmembrane TGF-beta-inducible protein, sequesters Smad proteins from active participation in TGF-beta signaling. Mol Cell. 2010 Jan 15;37(1):123-34. [Content Brief]

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