Prostate transmembrane protein, androgen induced 1 (PMEPA1)

PMEPA1 (Prostate transmembrane protein, androgen induced 1) is a highly conserved, type 1b transmembrane protein with luminal, membrane spanning, and cytoplasmic domains[2][4][6]. Induced by androgens and TGF-β, PMEPA1 serves as a critical regulator of both androgen receptor (AR) and TGF-β signaling pathways via negative feedback mechanisms[1][2][4][7]. It suppresses AR protein levels by facilitating ubiquitination (likely via NEDD4 E3 ligase recruitment) and inhibits canonical TGF-β/Smad transcription[1][4]. PMEPA1 is implicated in several solid tumors, particularly prostate cancer, where it may function as a tumor suppressor or promoter depending on context and isoform[2][4]. Reduced PMEPA1 expression is associated with increased AR signaling, poor prognosis, higher Gleason scores, and resistance to AR-targeted therapeutics[4]. PMEPA1 acts as both a biomarker and a potential therapeutic target, and its alternative splicing yields multiple functionally distinct isoforms[2][4][8]. It is tissue enhanced in prostate, with prognostic value in certain cancers[7]. Disease roles include direct involvement in cancer progression and associations with other pathologies such as aortic aneurysm and melanoma[1][7]. There are currently no well-established drugs that directly target PMEPA1[1][6].

Other names

TMEPAISTAG1Solid tumor-associated 1 proteinTransmembrane prostate androgen-induced proteinSolid tumor-associated gene 1Transmembrane, prostate androgen induced RNAProtein TMEPAI

Drugs targeting PMEPA1 (not well-established) would act through modulation of TGF-β signaling or AR degradation