TAGLN Is Downregulated by TRAF6-Mediated Proteasomal Degradation in Prostate Cancer Cells
TAGLN Is Downregulated by TRAF6-Mediated Proteasomal Degradation in Prostate Cancer Cells
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前列腺癌细胞中 TAGLN 受到 TRAF6 介导的蛋白酶体降解的下调。
DOI：
10.1158/1541-7786.mcr-20-0513
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发表时间：
2021-07-01
影响因子：
5.2
通讯作者：
Yang, Chenghua
中科院分区：
文献类型：
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作者：
Wen, Fuping;Sun, Xiaochen;Yang, Chenghua
Transgelin（TAGLN，也称为SM 22）是一种肌动蛋白相关蛋白，影响肌动蛋白丝的动力学。TAGLN的失调有助于不同癌症的发展，并且它通常被认为是肿瘤抑制因子。TAGLN通常在前列腺癌中下调;然而，TAGLN在前列腺癌中的详细功能以及TAGLN如何调节仍不清楚。在这项研究中，我们证实了TAGLN在前列腺癌组织中下调，并证明了TAGLN的下调通过蛋白酶体降解发生。接下来，我们发现TAGLN的表达水平与TRAF 6呈负相关。我们通过体外泛素化分析筛选了超过20对E2-E3对，发现E2 A-TRAF 6对催化TAGLN的单泛素化。然后，我们确定TAGLN的泛素化位点在K89或K108残基上，并证明K891 K108上TAGLN的泛素化对于TRAF 6介导的蛋白酶体降解是重要的。此外，我们研究了TAGLN在前列腺癌细胞中的功能。我们发现，TAGLN的消融促进前列腺癌细胞增殖，并通过激活NF-κ B和Myc信号通路抑制其迁移。总的来说，我们的研究为前列腺癌中TAGLN表达和活性的机制提供了新的见解。
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 K891 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-kappa B and Myc signaling pathways. Overall, our study provided new insights into the mechanisms underlying TAGLN expression and activity in prostate cancer.