首页> 外国专利> A METHOD FOR REGULATING CANCER STEM CELL GROWTH BY INHIBITING PHOSPHORYLATION OF 120TH THREONINE RESIDUE OF TSPYL5 PROTEIN, A COMPOSITION CONTAINING THE PEPTIDE SEQUENCE FUNCTIONING TO INHIBIT THE PHOSPHORYLATION AND A USE THEREOF

A METHOD FOR REGULATING CANCER STEM CELL GROWTH BY INHIBITING PHOSPHORYLATION OF 120TH THREONINE RESIDUE OF TSPYL5 PROTEIN, A COMPOSITION CONTAINING THE PEPTIDE SEQUENCE FUNCTIONING TO INHIBIT THE PHOSPHORYLATION AND A USE THEREOF

机译:通过抑制TSPYL5蛋白的120个苏氨酸残基的磷酸化来调节癌干细胞生长的方法,该成分包含肽序列,该肽序列具有抑制磷酸化的功能,及其用途

摘要

The present invention relates to a peptide suppressing the phosphorylation of threonine (T120), the 120th residue of TSPYL5 (testis-specific Y-like protein 5), which is specifically as follows. The present inventors constructed T120D, the mutant of the 120th residue threonine (T120) of TSPYL5, and T120A-TSPYL5 gene and then transfected cells with them in order to investigate the effect of phosphorylation on T120 residue. As a result, wild-type TSPYL5 and T120D moved into nucleus and stayed there. But in the case of T120A-TSPYL5, TSPYL5 did not move into nucleus and instead it was expressed only in cytoplasm. The protein could not bind to AKT, either. Instead, ubiquitination of TSPYL5 was increased but SUMOylation was inhibited. Also, the expressions of ALDH1-A1, -A3, CD44 gene and protein were reduced, and thereby the growth and metastasis of lung cancer cells were suppressed and sphere formation was reduced. Based on the observation above, the inventors constructed the peptide composed of the amino acid sequences represented by SEQ. ID. NO: 43 or NO: 44 that could inhibit phosphorylation of the 120th residue threonine of TSPYL5. The said peptide can be effectively used as a composition for the inhibition of cancer cell growth, metastasis, and cancer stem cell growth.
机译:本发明涉及一种抑制苏氨酸(T120)(TSPYL5的第120个残基)(睾丸特异性Y样蛋白5)的磷酸化的肽,其具体如下。本发明人构建了T120D,TSPYL5的第120残基苏氨酸(T120)的突变体和T120A-TSPYL5基因,然后用它们转染细胞,以研究磷酸化对T120残基的影响。结果,野生型TSPYL5和T120D移入细胞核并停留在那里。但是在T120A-TSPYL5的情况下,TSPYL5不会移入细胞核,而是仅在细胞质中表达。该蛋白质也无法与AKT结合。相反,TSPYL5的泛素化增加,但SUMOylation被抑制。而且,ALDH1-A1,-A3,CD44基因和蛋白质的表达减少,从而抑制了肺癌细胞的生长和转移,并减少了球的形成。基于上述观察,发明人构建了由SEQ.ID.No.1所示的氨基酸序列组成的肽。 ID。 NO:43或NO:44可能会抑制TSPYL5的第120个残基苏氨酸的磷酸化。所述肽可以有效地用作抑制癌细胞生长,转移和癌症干细胞生长的组合物。

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