A5038442456- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Mitochondrial Function and Pathology
- Genomics and Chromatin Dynamics
- Ubiquitin and proteasome pathways
- Nuclear Structure and Function
- Monoclonal and Polyclonal Antibodies Research
- DNA Repair Mechanisms
- Glycosylation and Glycoproteins Research
- Copyright and Intellectual Property
- DNA and Nucleic Acid Chemistry
- Estrogen and related hormone effects
- Receptor Mechanisms and Signaling
- Bacterial Genetics and Biotechnology
- COVID-19 impact on air quality
- Cellular transport and secretion
- ATP Synthase and ATPases Research
- Metabolism and Genetic Disorders
- Force Microscopy Techniques and Applications
- Antibiotic Resistance in Bacteria
- Retinoids in leukemia and cellular processes
- Genetics, Aging, and Longevity in Model Organisms
- Privacy, Security, and Data Protection
- Advanced Fluorescence Microscopy Techniques
- FOXO transcription factor regulation
California Institute of Technology
2018-2024
Children's Hospital of Pittsburgh
2024
University of Tennessee at Knoxville
2019-2024
University of Pittsburgh
2023
University of Alberta
2020
INTRODUCTION The subcellular compartmentalization of eukaryotic cells requires selective transport folded proteins and protein-nucleic acid complexes. Embedded in nuclear envelope pores, which are generated by the circumscribed fusion inner outer membranes, pore complexes (NPCs) sole bidirectional gateways for nucleocytoplasmic transport. ~110-MDa human NPC is an ~1000-protein assembly that comprises multiple copies ~34 different proteins, collectively termed nucleoporins. symmetric core...
In the mitochondrial outer membrane, α-helical transmembrane proteins play critical roles in cytoplasmic-mitochondrial communication. Using genome-wide CRISPR screens, we identified carrier homolog 2 (MTCH2), and its paralog MTCH1, showed that it is required for insertion of biophysically diverse tail-anchored (TA), signal-anchored, multipass proteins, but not membrane β-barrel proteins. Purified MTCH2 was sufficient to mediate into reconstituted proteoliposomes. Functional mutational...
INTRODUCTION In eukaryotic cells, the selective bidirectional transport of macromolecules between nucleus and cytoplasm occurs through nuclear pore complex (NPC). Embedded in envelope pores, ~110-MDa human NPC is an ~1200-Å-wide ~750-Å-tall assembly ~1000 proteins, collectively termed nucleoporins. Because NPC's eightfold rotational symmetry along nucleocytoplasmic axis, each ~34 different nucleoporins multiples eight. Architecturally, symmetric core composed inner ring encircling central...
Mitochondrial outer membrane ⍺-helical proteins play critical roles in mitochondrial-cytoplasmic communication, but the rules governing targeting and insertion of these biophysically diverse remain unknown. Here, we first defined complement required mammalian biogenesis machinery through genome-wide CRISPRi screens using topologically distinct proteins. Systematic analysis nine identified factors across 21 substrates reveals that components are organized into pathways act on based their...
The "Mlx" and "Myc" transcription factor networks cross-communicate share many common gene targets. Myc's activity depends upon its heterodimerization with Max, whereas the Mlx Network requires that Max-like associate Myc-like factors MondoA or ChREBP. current work demonstrates body-wide inactivation, like of Myc, accelerates numerous aging-related phenotypes pertaining to body habitus metabolism. deregulation Myc target sets is also accelerated. Among other functions, these often regulate...
The MYC oncoprotein regulates numerous genes involved in cellular processes such as cell cycle and mitochondrial ribosomal structure function. This requires heterodimerization with its partner, MAX, binding to specific promoter enhancer elements. Here, we show that MAX also bind near transcriptional end sites (TESs) of over one-sixth all annotated genes. These interactions are dose-dependent, evolutionarily conserved, stabilize the normally short-lived protein regulate expression both...
Abstract The nuclear pore complex (NPC) is the sole bidirectional gateway for nucleocytoplasmic transport. Despite recent progress in elucidating arrangement of structured scaffold building blocks NPC symmetric core, their cohesion by multivalent unstructured linker proteins remained elusive. Combining biochemical reconstitution, high resolution structure determination, docking into cryo-electron tomographic reconstructions, and physiological validation, we elucidated architecture entire...
Abstract Native isolation of proteins in high yield and purity is a major bottleneck for analysis their three- dimensional structure, function, interactome. Here, we present streamlined workflow the rapid production or protein complexes using lentiviral transduction human suspension cells, combined with highly-specific nanobody-mediated purification proteolytic elution. (1) First, generation plasmid coding interest fused to an N- C- terminal GFP ALFA peptide tag rapidly achieved toolkit have...
Librarians serve as defenders of intellectual freedom and social responsibility, this includes speaking out against censorship. Censorship information, materials, books occurs in the public, but censorship can also occur libraries themselves. Those impacted most by are marginalized communities, such LGBTQ+ community. The purpose paper is to explore how internal, external institutional affects community what librarians do uphold their defense Internal, or self-censorship, at librarian level...
Optimal gene transcription is achieved through precise interactions between factors and their DNA binding sites. We provide evidence that conserved distally located 5′-flanking sequences interact directly with the intrinsically disordered amino-terminal region of thyroid receptor-α (TRα) to control transcriptional activity. Simulated modeling dynamics multiple ChIP-seq–derived consistently reveal specific lysine/arginine–DNA minor groove interactions. The impact these distort structural...
Abstract In the mitochondrial outer membrane, tail-anchored (TA) proteins play critical roles in cytoplasmic-mitochondrial communication. Using genome-wide CRISPRi screens, we identify factors involved TA biogenesis human cells. We show that MTCH2, and its paralog MTCH1, are required for insertion of biophysically diverse TAs, but not membrane β-barrel proteins. a reconstituted system, purified MTCH2 is sufficient to mediate into proteoliposomes. Functional mutational studies reveal uses...
MYC proto-oncogene dysregulation alters metabolism, translation and other functions in ways that support tumor induction maintenance. Although Myc+/- mice are healthier longer-lived than control mice, the long-term ramifications of more complete Myc loss remain unknown. We now describe chronic consequences body-wide inactivation initiated post-natally. “MycKO” acquire numerous features premature aging including altered body composition habitus, metabolic dysfunction, hepatic steatosis gene...
SUMMARY Mitochondrial outer membrane ⍺-helical proteins play critical roles in mitochondrial-cytoplasmic communication, but the rules governing targeting and insertion of these biophysically diverse substrates remain unknown. Here, we first defined complement required mammalian biogenesis machinery through genome-wide CRISPRi screens using topologically distinct proteins. Systematic analysis nine identified factors across 21 reveals that components are organized into pathways which act on...
Nuclear hormone receptors (NR) are transcription factors that relay cellular signals through distinct multiprotein assemblies. Hormonal produce structural changes within NRs determine the composition of interacting proteins. characteristically modular At N terminus is an intrinsically disordered N-terminal domain (NTD) followed by a DNA-binding (DBD). The DBD recognizes DNA sites at promoter specific genes. C ligand-binding (LBD) which also contains dimerization interface. Agonist binding to...