Prostate transmembrane protein androgen induced 1 (PMEPA1) (PMEPA1)

Prostate transmembrane protein androgen induced 1 (PMEPA1), also known as TMEPAI, is a type I transmembrane protein that serves as a critical negative feedback regulator of the Transforming Growth Factor-beta (TGF-beta) and androgen receptor (AR) signaling pathways (UniProt Q969W9). It functions by sequestering SMAD proteins and recruiting E3 ubiquitin ligases, such as NEDD4, to promote the degradation of TGF-beta receptors, thereby limiting the duration and intensity of TGF-beta signaling (PMID: 21135544). In various cancers, PMEPA1 expression is frequently dysregulated; it is often overexpressed in breast and colorectal cancers where it promotes tumor progression and metastasis by inhibiting TGF-beta-mediated growth arrest (PMID: 30333564). Conversely, in prostate cancer, its expression is often lost during the transition to androgen independence, leading to hyperactivation of AR signaling (PMID: 25605863). Because of its central role in controlling key oncogenic pathways and its influence on protein stability, PMEPA1 is considered a promising therapeutic target for solid tumors. Experimental strategies currently include the use of siRNA and antisense oligonucleotides to modulate its expression in preclinical models. However, the pleiotropic nature of the TGF-beta pathway means that targeting PMEPA1 requires careful consideration of potential systemic side effects and the specific cellular context.

Other names

TMEPAISTAG1ERG1.2Transmembrane prostate androgen-induced protein

Negative feedback regulation of TGF-beta signaling via SMAD sequestration and NEDD4-mediated degradation of TGF-beta receptors.