Abstract

Transgelin (TAGLN, also named SM22) is an actin-associated protein and affects dynamics of actin filaments. Deregulation of TAGLN contributes to the development of different cancers, and it is commonly considered to be a tumor suppressor. TAGLN is usually downregulated in prostate cancer; however, the detailed functions of TAGLN in prostate cancer and how TAGLN is regulated remains unclear. In this study, we confirmed that TAGLN is downregulated in prostate cancer tissues and demonstrated that the downregulation of TAGLN occurs through proteasomal degradation. Next, we found that the expression level of TAGLN is inversely correlated with TRAF6. We screened more than 20 E2–E3 pairs by in vitro ubiquitination assay and found that the E2A–TRAF6 pair catalyzed mono ubiquitination of TAGLN. We then identified the ubiquitination sites of TAGLN to be on K89 or K108 residues and demonstrated that ubiquitination of TAGLN on K89/K108 are important for TRAF6-mediated proteasomal degradation. Furthermore, we investigated the function of TAGLN in prostate cancer cells. We found that ablation of TAGLN promoted prostate cancer cell proliferation and suppressed their migration via activation of NF-κB and Myc signaling pathways. Overall, our study provided new insights into the mechanisms underlying TAGLN expression and activity in prostate cancer. Implications: E3 ligase TRAF6 mediate mono-ubiquitination and degradation of TAGLN, which leads to activation of NF-κB and Myc signaling pathways in prostate cancer cells.