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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Chandu, Dilip Quatrano, Ralph S. Khandelwal, Abha Roe, Catherine M. Kopan, Raphael |
| Description | Author Affiliation: Khandelwal A ( Department of Biology, Washington University, St. Louis, MO 63110, USA.); |
| Abstract | Presenilins (PS) provide the catalytic activity for gamma-secretase, which cleaves physiologically relevant substrates including Notch, ErbB4, and APP. Recent genetic studies indicated that the contribution of PS1 to mouse development includes gamma-secretase-independent functions that cannot be easily explained by any of the demonstrated or hypothesized functions of this protein. To begin a nonbiased analysis of PS1 activity unencumbered by the dominant effect stemming from loss of Notch function, we characterized PS functions in the early land plant Physcomitrella patens, which lacks Notch, ErbB4, and APP. Removal of P. patens PS resulted in phenotypic abnormalities. Further assays performed to delineate the defective pathways in PS-deficient P. patens implicated improper function of the cytoskeletal network. Importantly, this characterization of a nonmetazoan PS uncovered a previously undescribed, evolutionarily conserved function (human PS1 can rescue the growth and light responses) that is gamma-secretase-independent (mutants with substitutions of the catalytic aspartyl residues retain the activity). Introduction of PpPS into PS-deficient mouse embryonic fibroblasts rescues normal growth rates, demonstrating that at least some metazoan functions of PS are evolutionarily conserved. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 33 |
| Volume Number | 104 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2007-08-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Amyloid Precursor Protein Secretases Metabolism Biological Evolution Plants Presenilins Physiology Gene Silencing Phenotype RNA Interference Recombination, Genetic Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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