c-Abl and Arg tyrosine kinases regulate lysosomal degradation of the oncoprotein Galectin-3
c-Abl and Arg tyrosine kinases regulate lysosomal degradation of the oncoprotein Galectin-3
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c-Abl 和 Arg 酪氨酸激酶调节癌蛋白 Galectin-3 的溶酶体降解
DOI：
10.1038/cdd.2010.8
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发表时间：
2010-08-01
影响因子：
12.4
通讯作者：
Cao, C.
中科院分区：
文献类型：
--
作者：
Li, X.;Ma, Q.;Cao, C.
Galectin-3(Galectin-3，Galectin-3)在肿瘤的转移和转移中起重要作用。本研究表明，c-Abl和Abl相关基因(Arg)与Gal3结合并使其磷酸化。C-Abl/Arg的SH(Src Homology)3结构域与Gal3的P(80)GPPSGP基序结合，Tyr79和Tyr118是主要的酪氨酸磷酸化位点。这种相互作用和磷酸化的结果是伴侣介导的Gal3自噬显著受损。表达Gal3的细胞和经c-Abl/Arg抑制剂STI571处理的细胞、Gal3缺失的细胞和表达Gal3磷酸化突变体的Gal3缺失的细胞都表现出对凋亡诱导剂的敏感性增加。此外，表达磷酸化突变体的肿瘤细胞显示出致瘤性受损。这些结果部分解释了Abl和Arg的抗细胞凋亡作用。由于肿瘤经常过度表达Gal3，一种c-Abl/Arg特异性抑制剂可能与其他抗肿瘤药物一起应用于肿瘤治疗中针对Gal3溶酶体的降解。《细胞死亡与分化》(2010年)1712771287DOI：10.1038/cdd.2010.8；2010年2月12日在线发布
Galectin-3 (Gal3) has important roles in tumor transformation and metastasis. This study shows that c-Abl and Abl-related gene (Arg) associate with and phosphorylate Gal3. The SH (Src homology) 3 domains of c-Abl/Arg bind to a P(80)GPPSGP motif of Gal3, and Tyr79 and Tyr118 are the major tyrosine phosphorylation sites. A consequence of this interaction and phosphorylation is the significant impairment of chaperone-mediated autophagy of Gal3. Cells expressing Gal3 and treated with the c-Abl/Arg inhibitor STI571, Gal3-depleted cells, and Gal3-depleted cells expressing Gal3 phosphorylation mutants all display an increased sensitivity to apoptosis-inducing agents. In addition, tumor cells expressing the phosphorylation mutants show impaired tumorigenicity. These results partially explain the antiapoptotic effect of Abl and Arg. As tumors frequently overexpress Gal3, a c-Abl/Arg-specific inhibitor may potentially be applied along with other antitumor drugs to target the lysosomal degradation of Gal3 in tumor therapy. Cell Death and Differentiation (2010) 17, 1277-1287; doi:10.1038/cdd.2010.8; published online 12 February 2010