Molecular regulation, membrane association and secretion of tumor cathepsin B.
Upregulation, membrane association and secretion of cathepsin B have been shown to occur in many types of tumors and to correlate positively with their invasive and metastatic capabilities. To further understand changes in cathepsin B activity and localization, we have been examining its regulation at many levels including transcription and trafficking. Our studies indicate that there may be three promoter regions in the cathepsin B gene. Of these, continued examination of the promoter upstream of exon 1 has indicated possible control by several regulatory factors including E-box and Sp-1 binding elements. Upregulation of cathepsin B at this level may account for some of the secretion of cathepsin B found in tumors. We have also gathered evidence that endo- and exocytosis of cathepsin B may be regulated by ras and ras-related proteins in addition to previously described trafficking systems. There is also evidence that several populations of lysosomes may exist and that trafficking to different populations may determine whether cathepsin B is secreted from the tumor cell or remains intracellular. Our results indicate that membrane association and secretion of cathepsin B is not a random process in the tumor cell, but rather part of a tightly controlled system.
Frosch
B A
BA
Department of Pharmacology and Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Berquin
I
I
Emmert-Buck
M R
MR
Moin
K
K
Sloane
B F
BF
D000818:Animals; D002401:Cathepsin B / Q000235:genetics* / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology*; D006801:Humans; D009369:Neoplasms / Q000201:enzymology*; D011401:Promoter Regions, Genetic; D016385:TATA Box; D014158:Transcription, Genetic
D002401:Cathepsin B