Characterization of an Atypical γ-Secretase Complex from Hematopoietic Origin Journal Article
| Authors: | Placanica, L.; Chien, J. W.; Li, Y. M. |
| Article Title: | Characterization of an Atypical γ-Secretase Complex from Hematopoietic Origin |
| Abstract: | γ-Secretase is a widely expressed multisubunit enzyme complex which is involved in the pathogenesis of Alzheimer disease and hematopoietic malignancies through its aberrant processing of the amyloid precursor protein (APP) and Notch 1, respectively. While γ-secretase has been extensively studied, there is a dearth of information surrounding the activity, composition, and. function of γ-secretase expressed in distinct cellular populations. Here we show that endogenous γ-secretase complexes of hematopoietic origin are distinct from, epithelial derived γ-secretase complexes. Hematopoietic γ-secretase has reduced activity for APP and Notchl processing compared to epithelial, γ-secretase. Characterization of the active complexes with small molecule affinity probes reveals that hematopoietic γ-secretase has an atypical, subunit composition with significantly altered subunit stoichiometry. Furthermore, we demonstrate that these discrete complexes exhibit cell-line specific substrate selectivity suggesting a possible mechanism of substrate regulation. These data underscore the need for studying endogenous γ-secretase to fully understand of the biology of γ-secretase and its complexity as a molecular target for the development of disease therapeutics. © 2010 American Chemical Society. |
| Keywords: | controlled study; human cell; biology; cell line; receptor, notch1; enzyme activity; enzyme substrate; enzyme analysis; substrate specificity; hematopoietic cell; epithelial cells; blood cells; epithelium; protein subunits; alzheimer disease; sulfur compounds; amyloid precursor protein; notch1 receptor; amyloid precursor protein secretases; stoichiometry; active complexes; small molecules; gamma secretase; molecular targets; amyloid beta-protein precursor; amyloid precursor proteins; discrete complexes; multi-subunit enzymes; secretase complex; secretases; substrate selectivity; pumping plants |
| Journal Title: | Biochemistry |
| Volume: | 49 |
| Issue: | 13 |
| ISSN: | 0006-2960 |
| Publisher: | American Chemical Society |
| Date Published: | 2010-04-06 |
| Start Page: | 2796 |
| End Page: | 2804 |
| Language: | English |
| DOI: | 10.1021/bi901388t |
| PUBMED: | 20178366 |
| PROVIDER: | scopus |
| PMCID: | PMC2880330 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 4" - "Export Date: 20 April 2011" - "CODEN: BICHA" - "Source: Scopus" |
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