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
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    发明申请
    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 审中-公开
    一种通过抑制TSPYL5蛋白质的第120位残基的磷酸化来调节癌症干细胞生长的方法,所述TSPYL5蛋白质是一种含肽功能抑制磷酸化作用的肽组合物及其用途

    公开(公告)号:WO2017217782A1

    公开(公告)日:2017-12-21

    申请号:PCT/KR2017/006240

    申请日:2017-06-15

    IPC分类号: C07K7/08 C12N5/095 A61K38/10

    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.

    摘要翻译: 本发明涉及抑制TSPYL5(睾丸特异性Y样蛋白5)的第120个残基苏氨酸(T120)磷酸化的肽,具体如下。 本发明人构建了T120D,TSPYL5的第120个残基苏氨酸(T120)和T120A-TSPYL5基因的突变体,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进入细胞核并停留在那里。 但在T120A-TSPYL5的情况下,TSPYL5不进入细胞核,而是仅在细胞质中表达。 蛋白质也不能与AKT结合。 相反,TSPYL5泛素化增加,但SUMO化受到抑制。 此外,ALDH1-A1,-A3,CD44基因和蛋白质的表达降低,由此肺癌细胞的生长和转移受到抑制并且球形成减少。 基于上述观察,本发明人构建了由SEQ.ID.No.1所代表的氨基酸序列组成的肽。 ID。 NO:43或NO:44可抑制TSPYL5的第120位苏氨酸的磷酸化。 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。