Premium
Molecular regulation, membrane association and secretion of tumor cathepsin B
Author(s) -
FROSCH BARBARA A.,
BERQUIN ISABELLE,
EMMERTBUCK MICHAEL R.,
MOIN KAMIAR,
SLOANE BONNIE F.
Publication year - 1999
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1111/j.1699-0463.1999.tb01523.x
Subject(s) - cathepsin b , secretion , downregulation and upregulation , cathepsin s , cathepsin e , cathepsin , biology , cathepsin l , microbiology and biotechnology , cathepsin d , cathepsin h , cathepsin o , gene , biochemistry , enzyme
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 I 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.