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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Tucker Zhou, Tracey B. Abraham, Carmela R. King, Gwendalyn D. Chen, Cidi |
| Description | Author Affiliation: Tucker Zhou TB ( From the Departments of Pharmacology and Experimental Therapeutics and.) |
| Abstract | Klotho (KL) is an age-regulating protein named after the Greek goddess who spins the thread of life. Mice deficient in KL are normal throughout development, but rapidly degenerate and display a variety of aging-associated abnormalities that eventually lead to decreased life expectancy. While multiple genetic association studies have identified KL polymorphisms linked with changes in disease risk, there is a paucity of concrete mechanistic data to explain how these amino acid substitutions alter KL protein function. The KLVS polymorphism is suggested to lead to changes in protein trafficking although the mechanism is unclear. Our studies have sought to further investigate the functional differences in the KLVS variant that result in increased risk of many age-related diseases. Our findings suggest that the F352V and C370S substitutions lead to alterations in processing as seen by differences in shedding and half-life. Their co-expression in KLVS results in a phenotype resembling wild-type, but despite this intragenic complementation there are still changes in homodimerization and interactions with FGFR1c. Taken together, these studies suggest that KLVS leads to altered homodimerization that indirectly leads to changes in processing and FGFR1c interactions. These findings help elucidate the functional differences that result from the VS polymorphism, which will help clarify how alterations in KL function can lead to human disease and affect cognition and lifespan. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 51 |
| Volume Number | 288 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2013-12-20 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Aging Genetics Glucuronidase Metabolism Polymorphism, Single Nucleotide Aging, Premature Genetic Predisposition To Disease HEK293 Cells Mutation, Missense Protein Multimerization Protein Transport Receptor, Fibroblast Growth Factor, Type 1 Research Support, N.I.H., Extramural Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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