title: CDK5 activator p35 downregulates E-cadherin precursor independently of CDK5.
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.
authors.affiliation: Key Laboratory of Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Fujian 361005, China.
authors.forename: Shuyong
authors.initials: S
authors.lastname: Lin
authors.forename: Jifeng
authors.initials: J
authors.lastname: Wang
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Ye
authors.forename: Nancy Y
authors.initials: NY
authors.lastname: Ip
authors.forename: Sheng-Cai
authors.initials: SC
authors.lastname: Lin
mesh_terms: D002460:Cell Line; D051360:Cyclin-Dependent Kinase 5 / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology*; D006801:Humans
chemical_list: D051360:Cyclin-Dependent Kinase 5