首页> 外国专利> TSPYL5 120 Method to block the growth of cancer stem cells via inhibiting the phosphorylation of 120th threonine residue in TSPYL5 and Peptide inhibitor and the use thereof

TSPYL5 120 Method to block the growth of cancer stem cells via inhibiting the phosphorylation of 120th threonine residue in TSPYL5 and Peptide inhibitor and the use thereof

机译:TSPYL5 120通过抑制TSPYL5和肽抑制剂中第120苏氨酸残基的磷酸化来阻止癌症干细胞生长的方法及其用途

摘要

The present invention relates to a peptide which inhibits phosphorylation of the 120th threonine residue of TSPYL5 (Testis-specific Y-like protein 5) protein. The T120D and T120A-TSPYL5 mutations of the 120th threonine (T120) residue of TSPYL5 were transformed into the cells to confirm the effect of phosphorylation of T120 residues. As a result, normal TSPYL5 and T120D migrated into the nucleus However, in the case of T120A, it was confirmed that TSPYL5 protein did not migrate into the nucleus but was expressed only in cytoplasm, could not bind AKT, increased ubiquitination of TSPYL5 protein and suppressed sumoylation, ALDH1-A1, -A3, CD44 gene and protein expression, decreased the growth and metastasis of lung cancer cells, and decreased sphere formation. Based on this, a peptide consisting of the amino acid sequence of SEQ ID NO: 43 or SEQ ID NO: 44 of the present invention which inhibits the phosphorylation of the 120th threonine residue of TSPYL5 has been devised and they have been useful as cancer stem cell growth or metastasis or cancer stem cell growth inhibitor composition Can be used.
机译:本发明涉及抑制TSPYL5(睾丸特异性Y样蛋白5)蛋白的第120个苏氨酸残基磷酸化的肽。 TSPYL5的第120个苏氨酸(T120)残基的T120D和T120A-TSPYL5突变被转化到细胞中,以证实T120残基的磷酸化作用。结果,正常的TSPYL5和T120D迁移到细胞核中。但是,在T120A的情况下,证实TSPYL5蛋白没有迁移到细胞核中,仅在细胞质中表达,不能结合AKT,TSPYL5蛋白的泛素化增加,并且抑制SUMO化,ALDH1-A1,-A3,CD44基因和蛋白质表达,降低肺癌细胞的生长和转移,并减少球的形成。基于此,已经设计了由本发明的SEQ ID NO:43或SEQ ID NO:44的氨基酸序列组成的肽,其抑制TSPYL5的120个苏氨酸残基的磷酸化,并且已经用作癌症干。可以使用细胞生长或转移或癌症干细胞生长抑制剂组合物。

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