Regulation of the oncogenic activity of BCR-ABL by a tightly bound substrate protein RIN1
Regulation of the oncogenic activity of BCR-ABL by a tightly bound substrate protein RIN1
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DOI：
10.1016/s1074-7613(00)80452-5
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发表时间：
1997-06-01
期刊：
影响因子：
32.4
通讯作者：
Colicelli, J
中科院分区：
文献类型：
--
作者：
Afar, DEH;Han, LM;Colicelli, J
RIN1最初是通过其物理结合和干扰酵母中活化的Ras的能力而确定的。矛盾的是，RIN1增强造血细胞中BCR-ABL酪氨酸激酶的致癌活性，并显著加速BCR-ABL诱导的小鼠白血病。RIN1以不同于细胞周期调节因子c-Myc和cyclin D1以及Ras连接器She的方式拯救BCR-ABL突变体进行转化。这些生物学效应需要酪氨酸磷酸化RIN1，并将RIN1结合到Abl-SH2和SH3结构域。在人和小鼠白血病细胞中，RIN1被酪氨酸磷酸化并与BCR-ABL相关。RIN1是一类新的效应分子，依赖于胞质酪氨酸激酶的SH3、SH2和催化结构域的协同作用。
RIN1 was originally identified by its ability to physically bind to and interfere with activated Ras in yeast. Paradoxically, RIN1 potentiates the oncogenic activity of the BCR-ABL tyrosine kinase in hematopoietic cells and dramatically accelerates BCR-ABL-induced leukemias in mice. RIN1 rescues BCR-ABL mutants for transformation in a manner distinguishable from the cell cycle regulators c-Myc and cyclin D1 and the Ras connector She. These biological effects require tyrosine phosphorylation of RIN1 and binding of RIN1 to the Abl-SH2 and SH3 domains. RIN1 is tyrosine phosphorylated and is associated with BCR-ABL in human and murine leukemic cells. RIN1 exemplifies a new class of effector molecules dependent on the concerted action of the SH3, SH2, and catalytic domains of a cytoplasmic tyrosine kinase.