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Nuclear beta-catenin displays GSK-3beta- and APC-independent proteasome sensitivity in melanoma cells.
- Source :
-
Biochimica et biophysica acta [Biochim Biophys Acta] 2000 Feb 28; Vol. 1495 (3), pp. 308-18. - Publication Year :
- 2000
-
Abstract
- Colon carcinoma and melanoma cells containing either a deletion of the adenomatous polyposis coli tumor suppressor protein (APC) or mutation of the site in beta-catenin phosphorylated by glycogen synthase kinase-3beta (GSK-3beta) display elevated levels of detergent-soluble beta-catenin due to insensitivity of the cytosolic protein to proteasome-dependent degradation. In this study, we have examined the effect of beta-catenin mutation (S37F) or APC loss on the proteasome sensitivity of additional subcellular beta-catenin pools in melanoma cells. In contrast to detergent-soluble beta-catenin, the detergent-insoluble protein remains proteasome-sensitive irrespective of S37F mutation or APC status. This insoluble component appears associated primarily with nuclear cytoskeletal elements. In addition, DNase I treatment solubilized a portion of detergent-insoluble beta-catenin, suggesting that this fraction also contains chromatin-associated protein, and correlating with a proteasome-sensitive elevation in beta-catenin-stimulated reporter activity. Since the detergent-insoluble nuclear component of beta-catenin displays GSK-3beta- and APC-independent proteasome sensitivity, distinct from the soluble nuclear and cytosolic pools of this protein, regulation of beta-catenin proteasome sensitivity and the contribution of this process to beta-catenin function may be more complex than previously appreciated.
- Subjects :
- Adenomatous Polyposis Coli Protein
Cell Nucleus metabolism
Chromatin metabolism
Detergents chemistry
Glycogen Synthase Kinase 3
Glycogen Synthase Kinases
Humans
Melanoma
Multienzyme Complexes antagonists & inhibitors
Proteasome Endopeptidase Complex
Solubility
Subcellular Fractions metabolism
Tumor Cells, Cultured
beta Catenin
Calcium-Calmodulin-Dependent Protein Kinases metabolism
Cysteine Endopeptidases metabolism
Cytoskeletal Proteins metabolism
Multienzyme Complexes metabolism
Trans-Activators
Subjects
Details
- Language :
- English
- ISSN :
- 0006-3002
- Volume :
- 1495
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta
- Publication Type :
- Academic Journal
- Accession number :
- 10699468
- Full Text :
- https://doi.org/10.1016/s0167-4889(99)00162-7