Late cornified envelope 1C (LCE1C), a transcriptional target of TAp63 phosphorylated at T46/T281, interacts with PRMT5.
Late cornified envelope 1C (LCE1C), a transcriptional target of TAp63 phosphorylated at T46/T281, interacts with PRMT5.
复制标题
DOI：
10.1038/s41598-018-23045-7
复制
发表时间：
2018-03-20
影响因子：
4.6
通讯作者：
Nojima H
中科院分区：
文献类型：
--
作者：
Yabuta N;Ota C;Sasakura T;Naito Y;Okuzaki D;Fukushima K;Nojima H
P63是一种属于P53家族的转录因子，调节表皮分化、干细胞分化、细胞死亡、肿瘤发生、转移和衰老。然而，其分子机制仍不清楚。我们在这里报道，TAp63在T46/T281处磷酸化，特异性上调晚期角化包膜1C(LCE1C)基因，该基因在相对较晚的上皮发育阶段是必不可少的。我们在体外寻找细胞周期蛋白G相关激酶(GAK)靶标的过程中发现了这些磷酸化位点。依赖强力霉素的Myc-TAp63野生型蛋白表达显著上调LCE1C。利用LCE1C基因启动子区域的荧光素酶报告基因分析证实，TAp63-T46/T281的磷酸化有助于LCE1C基因的完全转录激活。LCE1C与精氨酸甲基转移酶5(PRMT5)蛋白相互作用，并将其从细胞核移位到细胞质。质谱学和免疫共沉淀鉴定Importin-α是LCE1C的结合伙伴之一。综上所述，我们认为GAK_TAp63-pT46/pT281_LCE1C轴在阻止PRMT5核功能中起重要作用。
p63, a transcriptional factor that belongs to the p53 family, regulates epidermal differentiation, stemness, cell death, tumorigenesis, metastasis, and senescence. However, its molecular mechanism remains elusive. We report here that TAp63 phosphorylated at T46/T281 specifically upregulates the late cornified envelope 1C (LCE1C) gene that is essential at a relatively late stage of epithelial development. We identified these phosphorylation sites during a search for the targets of Cyclin G-associated kinase (GAK) in vitro. LCE1C was drastically upregulated by doxycycline-dependent expression of Myc-TAp63 wild-type protein. Luciferase reporter assays using the promoter region of the LCE1C gene confirmed that the phosphorylations of TAp63-T46/T281 contributed to full transcriptional activation of the LCE1C gene. LCE1C interacted with protein arginine methyltransferase 5 (PRMT5) and translocated it from the nucleus to the cytoplasm. Mass spectrometry and co-immunoprecipitation identified importin-α as one of the association partners of LCE1C. In summary, we propose that the GAK_TAp63-pT46/pT281_LCE1C axis plays an important role in preventing the nuclear function of PRMT5.
登录
查看更多内容
影响因子：
64.5
作者：
Deutsch GB;Zielonka EM;Coutandin D;Weber TA;Schäfer B;Hannewald J;Luh LM;Durst FG;Ibrahim M;Hoffmann J;Niesen FH;Sentürk A;Kunkel H;Brutschy B;Schleiff E;Knapp S;Acker-Palmer A;Grez M;McKeon F;Dötsch V
通讯作者：
Dötsch V
DOI：
10.1111/j.1525-1438.2006.00638.x
发表时间：
2006-07-01
影响因子：
4.8
作者：
Lin, Z.;Nan, Y.;Kim, I.
通讯作者：
Kim, I.
影响因子：
9
作者：
通讯作者：
--
影响因子：
8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Mills, AA;Zheng, BH;Bradley, A
通讯作者：
Bradley, A