TMEPAI promotes degradation of the NF-?B signaling pathway inhibitory protein I?B? and contributes to tumorigenesis

The transmembrane prostate androgen-induced protein (TMEPAI) is known to be highly expressed in various types of cancer and promoted oncogenic abilities. However, the mechanisms whereby TMEPAI facilitates tumorigenesis are not fully understood. Here we reported that expression of TMEPAI activated the NF-kappa B signaling. TMEPAI showed direct interaction with NF-kappa B pathway inhibitory protein I kappa B alpha. Though ubiquitin ligase Nedd4 (neural precursor cell expressed, developmentally down-regulated 4) did not interact with I kappa B alpha directly, TMEPAI recruited Nedd4 for ubiquitination of I kappa B alpha, leading to I kappa B alpha degradation through the protea-somal and lysosomal pathway, and promoted activation of NF-kappa B signaling. Further study indicated NF-kappa B signaling is involved in TMEPAI-induced cell proliferation and tumor growth in immune deficient mice. This finding helps to further understand the mechanism of TMEPAI on tumorigenesis and suggests TMEPAI is po-tential target for cancer treatment.

Automated summary

The transmembrane prostate androgen-induced protein (TMEPAI) is highly expressed in various types of cancer and activates the NF-kappa B signaling pathway through the ubiquitination of I kappa B alpha. This results in the degradation of I kappa B alpha and the subsequent activation of NF-kappa B signaling. Further investigation revealed that TMEPAI-induced cell proliferation and tumor growth in immune deficient mice are mediated by the NF-kappa B signaling pathway. This study provides valuable insights into the role of TMEPAI in tumorigenesis and suggests it as a potential target for cancer treatment.