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Dbc1/Ccar2 And Ccar1 Are Largely Disordered Proteins That Have Evolved From One Common Ancestor, Jessica Brunquell, Jia Yuan, Aqeela Erwin, Sandy D. Westerheid, Bin Xue

Molecular Biosciences Faculty Publications

Deleted in breast cancer 1 (DBC1, CCAR2, KIAA1967) is a large, predominantly nuclear, multidomain protein that modulates gene expression by inhibiting several epigenetic modifiers, including the deacetylases SIRT1 and HDAC3, and the methyltransferase SUV39H1. DBC1 shares many highly conserved protein domains with its paralog cell cycle and apoptosis regulator 1 (CCAR1, CARP-1). In this study, we examined the full-length sequential and structural properties of DBC1 and CCAR1 from multiple species and correlated these properties with evolution. Our data shows that the conserved domains shared between DBC1 and CCAR1 have similar domain structures, as well as similar patterns of predicted disorder …

D-Beta-Hydroxybutyrate Extends Lifespan In , Clare Edwards, John Canfield, Neil Copes, Muhammad Rehan, David Lipps, Patrick C. Bradshaw

Molecular Biosciences Faculty Publications

The ketone body beta-hydroxybutyrate (βHB) is a histone deacetylase (HDAC) inhibitor and has been shown to be protective in many disease models, but its effects on aging are not well studied. Therefore we determined the effect of βHB supplementation on the lifespan ofC. elegans nematodes. βHB supplementation extended mean lifespan by approximately 20%. RNAi knockdown of HDACs hda-2 or hda-3 also increased lifespan and further prevented βHB-mediated lifespan extension. βHB-mediated lifespan extension required the DAF-16/FOXO and SKN-1/Nrf longevity pathways, the sirtuin SIR-2.1, and the AMP kinase subunit AAK-2. βHB did not extend lifespan in a genetic model of dietary restriction …

Inactivating Ube2m Impacts The Dna Damage Response And Genome Integrity Involving Multiple Cullin Ligases, Scott Cukras, Nicholas Morffy, Takbum Ohn, Younghoon Kee

Molecular Biosciences Faculty Publications

Protein neddylation is involved in a wide variety of cellular processes. Here we show that the DNA damage response is perturbed in cells inactivated with an E2 Nedd8 conjugating enzyme UBE2M, measured by RAD51 foci formation kinetics and cell based DNA repair assays. UBE2M knockdown increases DNA breakages and cellular sensitivity to DNA damaging agents, further suggesting heightened genomic instability and defective DNA repair activity. Investigating the downstream Cullin targets of UBE2M revealed that silencing of Cullin 1, 2, and 4 ligases incurred significant DNA damage. In particular, UBE2M knockdown, or defective neddylation of Cullin 2, leads to a blockade …

Relationship Between Gene Duplicability And Diversifiability In The Topology Of Biochemical Networks, Zhanyong Guo, Wen Jiang, Nuno Lages, Wade Borcherds, Degeng Wang

Molecular Biosciences Faculty Publications

Background: Selective gene duplicability, the extensive expansion of a small number of gene families, is universal. Quantitatively, the number of genes (P_(K)) with K duplicates in a genome decreases precipitously as K increases, and often follows a power law (P_(k)∝k^-α). Functional diversification, either neo- or sub-functionalization, is a major evolution route for duplicate genes.

Results: Using three lines of genomic datasets, we studied the relationship between gene duplicability and diversifiability in the topology of biochemical networks. First, we explored scenario where two pathways in the biochemical networks antagonize each other. Synthetic knockout of respective …

Evaluation Of A Method For Nitrotyrosine Site Identification And Relative Quantitation Using A Stable Isotope-Labeled Nitrated Spike-In Standard And High Resolution Fourier Transform Ms And Ms/Ms Analysis, Kent W. Seeley, Alison R. Fertig, Craig P. Dufresne, Joao P. C. Pinho, Stanley M. Stevens Jr.

Molecular Biosciences Faculty Publications

The overproduction of reactive oxygen and nitrogen species (ROS and RNS) can have deleterious effects in the cell, including structural and possible activity-altering modifications to proteins. Peroxynitrite is one such RNS that can result in a specific protein modification, nitration of tyrosine residues to form nitrotyrosine, and to date, the identification of nitrotyrosine sites in proteins continues to be a major analytical challenge. We have developed a method by which ¹⁵N-labeled nitrotyrosine groups are generated on peptide or protein standards using stable isotope-labeled peroxynitrite (O¹⁵NOO⁻), and the resulting standard is mixed with representative samples in …