A5024319715- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Endoplasmic Reticulum Stress and Disease
- Wnt/β-catenin signaling in development and cancer
- DNA Repair Mechanisms
- Genetics and Neurodevelopmental Disorders
- Peptidase Inhibition and Analysis
- Nuclear Structure and Function
- Influenza Virus Research Studies
- Organic Chemistry Cycloaddition Reactions
- Metal-Catalyzed Oxygenation Mechanisms
- SARS-CoV-2 and COVID-19 Research
- Enzyme-mediated dye degradation
- Toxin Mechanisms and Immunotoxins
- PARP inhibition in cancer therapy
- COVID-19 Clinical Research Studies
- RNA and protein synthesis mechanisms
- Fluorine in Organic Chemistry
- Autophagy in Disease and Therapy
- Hippo pathway signaling and YAP/TAZ
- Cancer-related Molecular Pathways
- Microbial bioremediation and biosurfactants
- Calcium signaling and nucleotide metabolism
Stanford University
2019-2024
Cyrus Biotechnology
2024
University of Washington
2014-2018
Seattle University
2016
Significance Ubiquitin fold modifier 1 (UFM1) is a ubiquitin-like posttranslational that essential for tissue development in metazoans. Genetic ablation of UFM1 or the genes encode enzymes conjugate to protein targets causes endoplasmic reticulum (ER) stress, suggesting role this modification ER homeostasis. Here, we show RPL26, largely uncharacterized ribosomal protein, primary cellular target UFMylation. Ribosomal RPL26 subject dynamic cycle UFMylation and de-UFMylation, catalyzed by are...
The epigenetic inheritance of DNA methylation requires UHRF1, a histone- and DNA-binding RING E3 ubiquitin ligase that recruits DNMT1 to sites newly replicated through ubiquitylation histone H3. UHRF1 binds with selectivity towards hemi-methylated CpGs (HeDNA); however, the contribution HeDNA sensing function remains elusive. Here, we reveal interaction is required for but dispensable chromatin interaction, which governed by reciprocal positive cooperativity between domains. recognition...
Protein UFMylation, i.e., post-translational modification with ubiquitin-fold modifier 1 (UFM1), is essential for cellular and endoplasmic reticulum homeostasis. Despite its biological importance, we have a poor understanding of how UFM1 conjugated onto substrates. Here, use rebuilding approach to define the minimal requirements protein UFMylation. We find that reported cognate E3 ligase UFL1 inactive on own instead requires adaptor UFBP1 form an active complex. Structure predictions suggest...
Poly(ADP-ribosyl)ation (PARylation) catalyzed by the tankyrase enzymes (Tankyrase-1 and -2; a.k.a. PARP-5a -5b) is involved in mitosis, telomere length regulation, GLUT-4 vesicle transport, cell growth differentiation. Together with E3 ubiquitin ligase RNF146 (a.k.a. Iduna), tankyrases regulate cellular levels of several important proteins including Axin, 3BP2, angiomotins, which are key regulators Wnt, Src Hippo signaling, respectively. These substrates first PARylated then ubiquitylated...
The tumor-suppressor protein BRCA1 works with BARD1 to catalyze the transfer of ubiquitin onto substrates. N-terminal regions and that contain their RING domains are responsible for dimerization ligase activity. This activity is a common feature among hundreds human domain-containing proteins. bind activate E2 ubiquitin-conjugating enzymes promote We show identity residues at specific positions in domain can tune levels up or down. report substitutions create structurally intact BRCA1/BARD1...
Tankyrase 1 (TNKS1; a.k.a. ARTD5) and tankyrase 2 (TNKS2; a.k.a ARTD6) are highly homologous poly(ADP-ribose) polymerases (PARPs) that function in a wide variety of cellular processes including Wnt signaling, Src Akt Glut4 vesicle translocation, telomere length regulation, centriole spindle pole maturation. proteins include sterile alpha motif (SAM) domain undergoes oligomerization vitro vivo. However, the SAM domains TNKS1 TNKS2 have not been structurally characterized mode is yet defined....
Abstract Protein UFMylation is emerging as a posttranslational modification essential for endoplasmic reticulum and cellular homeostasis. Despite its biological importance, we have poor understanding of how UFM1 conjugated onto substrates. Here, use rebuilding approach to define the minimal requirements protein UFMylation. We find that reported E3 ligase UFL1 inactive on own identify UFBP1 bind form an active complex. While UFC1 intrinsically Cys-reactive E2, do not any catalytic cysteines...
Ribosomes that stall while translating cytosolic proteins are incapacitated by incomplete nascent chains, termed "arrest peptides" (APs) destroyed the ubiquitin proteasome system (UPS) via a process known as ribosome-associated quality control (RQC) pathway. By contrast, APs on ribosomes translocating secretory into endoplasmic reticulum (ER-APs) shielded from cytosol ER membrane and tightly sealed ribosome-translocon junction (RTJ). How this is breached to enable access of UPS machinery 26S...