Inhibition of cathepsin L-induced degradation of epidermal growth factor receptors by c-Ha-ras gene products.
The inhibitory activities of c-Ha-ras gene products (p21s) toward several cysteine proteinases have been investigated. The activity of cathepsin L was inhibited by p21s most effectively while those of cathepsin B and papain were slightly inhibited by p21s. p21s did not show any inhibitory activity toward cathepsin H. In order to connect the protease-inhibitor activity of p21s with cell growth, the degradation of epidermal growth factor receptors (EGF-receptors) was investigated. EGF-receptors were preferentially cleaved by cathepsin L but not by cathepsin B or H. The cleavage of EGF-receptors by cathepsin L was inhibited by p21s dose-dependently. These results raise the possibility that p21s can suppress the degradation of growth-related proteins such as EGF-receptors and thereby affect cell growth.
Hiwasa
T
T
Division of Biochemistry, Chiba Cancer Center Research Institute, Japan.
Sakiyama
S
S
Yokoyama
S
S
Ha
J M
JM
Fujita
J
J
Noguchi
S
S
Bando
Y
Y
Kominami
E
E
Katunuma
N
N
D002294:Carcinoma, Squamous Cell; D002401:Cathepsin B / Q000037:antagonists & inhibitors / Q000378:metabolism; D056655:Cathepsin H; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism*; D011905:Genes, ras; D006801:Humans; D007118:Immunoassay; D010206:Papain / Q000037:antagonists & inhibitors; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000494:pharmacology*; D016283:Proto-Oncogene Proteins p21(ras); D012878:Skin Neoplasms; D014407:Tumor Cells, Cultured
D015853:Cysteine Proteinase Inhibitors; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; C534126:CTSH protein, human; D056655:Cathepsin H; D010206:Papain; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)