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Dr. Cohen’s laboratory is addressing the molecular basis of renal cancer, renal cystic disease and renal development and offers special expertise in gene expression mechanisms, signal transduction, protein-protein interactions, transcription factors, and renal epithelial cell biology. The laboratory has identified the first member of new protein family, the Jade family of proteins, on the basis of its interaction with the von Hippel-Lindau tumor suppressor pVHL. pVHL protein is a key component of the cellular oxygen-sensing system. VHL is also the major renal cancer gene in adults. Jade-1 is a novel, growth suppressive plant homeodomain transcription factor that is the first protein found to be stabilized by pVHL. Jade-1 is also a ubiquitin ligase and key component of histone acetylation complexes. Interestingly, Jade-1 is stabilized by VHL protein in a manner that correlates with risk of renal manifestations in von Hippel-Lindau disease, which includes a cystic renal disease phenotype. A wider role for Jade-1 in renal cyst formation was therefore sought. Jade-1 is regulated by the product of the major gene for autosomal dominant polycystic kidney disease (ADPKD), polycystin-1, in a manner that is also disease relevant and physiologic. Importantly, Jade-1 serves as a critical ubiquitin ligase for the oncoprotein beta-catenin, which also plays critical roles in renal cancer, renal cyst formation and renal development. In part by controlling transcription and beta-catenin ubiquitination, Jade-1 and related family members are likely to be particularly important in many contexts. .
Techniques:
Cancer biology and epithelial cell biology approaches, advanced molecular biology approaches, protein-protein interactions, yeast 2-hybrid screening, protein ubiquitination assays, protein-DNA interactions, transcription assays, gene expression mechanisms including microarrays, confocal microscopy, transgenic and knockout mice.
Research Interests
Papers共 38 篇Author StatisticsCo-AuthorSimilar Experts
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Acta neuropathologicano. 1 (2021): 33-53
Proceedings of the National Academy of Sciences of the United States of Americano. 3 (2016): 638-43
mag(2014)
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