Epidermal growth factor cytoplasmic domain affects ErbB protein degradation by the lysosomal and ubiquitin-proteasome pathway in human cancer cells.

ABSTRACT: The cytoplasmic domains of EGF-like ligands, including EGF cytoplasmic domain (EGFcyt), have important biological functions. Using specific constructs and peptides of human EGF cytoplasmic domain, we demonstrate that EGFcyt facilitates lysosomal and proteasomal protein degradation, and this coincided with growth inhibition of human thyroid and glioma carcinoma cells. EGFcyt and exon 22-23-encoded peptide (EGF22.23) enhanced procathepsin B (procathB) expression and procathB-mediated lysosomal degradation of EGFR/ErbB1 as determined by inhibitors for procathB and the lysosomal ATPase inhibitor BafA1. Presence of mbEGFctF, EGFcyt, EGF22.23, and exon 23-encoded peptides suppressed the expression of the deubiqitinating enzyme ubiquitin C-terminal hydrolase-L1 (UCH-L1). This coincided with hyper

SUBMITTER: Glogowska A 

PROVIDER: S-EPMC3384427 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature