CDK5 activator p35 downregulates E-cadherin precursor independently of CDK5 |
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Authors: | Lin Shuyong Wang Jifeng Ye Zhiyun Ip Nancy Y Lin Sheng-Cai |
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Affiliation: | Key Laboratory of Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Fujian 361005, China. |
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Abstract: | Dysfunction of E-cadherins often results in metastasis of cancerous cells. Here we show that p35, a critical regulator of cyclin-dependent kinase 5 (CDK5), specifically depletes the precursor form of E-cadherin, but not the mature form, by using a precursor-specific antibody. Most intriguingly, this downregulation of precursor E-cadherin by p35 is unequivocally independent of CDK5. Moreover, we found that p35 forms complexes with E-cadherin proteins. We also found that p35 co-expression can target E-cadherin to lysosomes and that p35-triggered disappearance of E-cadherin precursor can be blocked specifically by lysosomal protease inhibitors, indicating that p35 induces endocytosis and subsequent degradation of precursor E-cadherin. |
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Keywords: | CDK5, cyclin-dependent kinase 5 dn, dominant negative PCR, polymerase chain reaction |
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