A5031454601- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- Immunotherapy and Immune Responses
- RNA Interference and Gene Delivery
- DNA Repair Mechanisms
- RNA Research and Splicing
- Autophagy in Disease and Therapy
- CRISPR and Genetic Engineering
- Peptidase Inhibition and Analysis
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Cell death mechanisms and regulation
- Cellular transport and secretion
- Mitochondrial Function and Pathology
- Telomeres, Telomerase, and Senescence
- Parathyroid Disorders and Treatments
- Endoplasmic Reticulum Stress and Disease
- Histone Deacetylase Inhibitors Research
- Multiple Myeloma Research and Treatments
- Microtubule and mitosis dynamics
- Cancer-related Molecular Pathways
- Metabolism, Diabetes, and Cancer
- PARP inhibition in cancer therapy
- Heat shock proteins research
Amgen (United States)
2022-2025
The University of Texas Southwestern Medical Center
2007-2024
St. Jude Children's Research Hospital
2016-2024
Southwestern Medical Center
2007-2014
University of North Carolina at Chapel Hill
2003-2004
Endosomal protein recycling is a fundamental cellular process important for homeostasis, signaling, and fate determination that implicated in several diseases. WASH an actin-nucleating essential this process, its activity controlled through K63-linked ubiquitination by the MAGE-L2-TRIM27 ubiquitin ligase. Here, we show USP7 deubiquitinating enzyme integral component of ligase WASH-mediated endosomal actin assembly recycling. Mechanistically, acts as molecular rheostat to precisely fine-tune...
DNA repair is required for the genomic stability and well-being of an organism.In yeasts, a multisubunit complex consisting SMC5, SMC6, MMS21/NSE2, other non-SMC proteins through homologous recombination.The yeast MMS21 protein SUMO ligase.Here we show that human homolog also ligase.hMMS21 stimulates sumoylation hSMC6 TRAX.Depletion hMMS21 by RNA interference (RNAi) sensitizes HeLa cells toward damage-induced apoptosis.Ectopic expression wild-type hMMS21, but not its ligase-inactive mutant,...
Abstract Hepatocellular carcinoma (HCC) is one of the leading cause cancer death in world. Fructose-1,6-biphosphatase (FBP1), a rate-limiting enzyme gluconeogenesis, has been identified recently as tumor suppressor HCC and other types. In this study, we demonstrated that tripartite motif-containing protein 28 (TRIM28) binds directly to promotes FBP1 for ubiquitination degradation. MAGE-A3 MAGE-C2, which are known be overexpressed HCC, can enhance TRIM28-dependent degradation by forming...
Targeting cereblon (CRBN) is currently one of the most frequently reported proteolysis-targeting chimera (PROTAC) approaches, owing to favorable drug-like properties CRBN ligands, immunomodulatory imide drugs (IMiDs). However, IMiDs are known be inherently unstable, readily undergoing hydrolysis in body fluids. Here we show that and IMiD-based PROTACs rapidly hydrolyze commonly utilized cell media, which significantly affects their efficacy. We designed novel binders, phenyl glutarimide (PG)...
RNA-targeting small molecules (rSMs) have become an attractive modality to tackle traditionally undruggable proteins and expand the druggable space. Among many innovative concepts, chimeras (RNATACs) represent a new class of multispecific, induced proximity that act by chemically bringing RNA targets into with endogenous effector, such as ribonuclease (RNase). Depending on RNATACs can alter stability, localization, translation, or splicing target RNA. Although still in its infancy, this has...
In sympathetic neurons, unlike most nonneuronal cells, growth factor withdrawal–induced apoptosis requires the development of competence in addition to cytochrome c release activate caspases. Thus, although cells die rapidly with cytosolic alone, neurons are remarkably resistant unless they develop competence. We have identified endogenous X-linked inhibitor protein (XIAP) as essential postcytochrome regulator caspase activation these neurons. contrast wild-type that injection c,...
Autophagy is commonly altered in cancer and has a complicated, but important role regulation of tumor growth. often suppressive the early stages development, contributes to late Because this, putative oncogenes that modulate autophagy signaling are especially interesting. Here we discuss our recent work detailing function MAGEA-TRIM28 ubiquitin ligase as an oncogene product targets PRKAA1/AMPKα1 for ubiquitination proteasome-mediated degradation. Degradation AMPK, master cellular energy...
DNA double-strand breaks (DSBs) fuel cancer-driving chromosome translocations. Two related structural maintenance of chromosomes (Smc) complexes, cohesin and Smc5/6, promote DSB repair through sister chromatid homologous recombination (SCR). Here we show that the Smc5/6 subunit Mms21 sumoylates multiple lysines Scc1. promotes cohesin-dependent small ubiquitin-like modifier (SUMO) accumulation at laser-induced damage sites in S/G2 human cells. Cells expressing nonsumoylatable Scc1 mutant...
End resection of DNA double-strand breaks (DSBs) to generate 3'-single-stranded facilitates DSB repair via error-free homologous recombination (HR) while stymieing by the error-prone non-homologous end joining (NHEJ) pathway. Activation involves phosphorylation 5' 3' exonuclease EXO1 phosphoinositide 3-kinase-like kinases ATM (ataxia telangiectasia-mutated) and ATR (ATM Rad3-related) cyclin-dependent 1 2. After activation, must also be restrained prevent over-resection that is known hamper...
Mammals evolved testis-specific Mage-a genes to protect the male germline under starvation stress and are co-opted in cancer.
Prader-Willi syndrome (PWS) is a developmental disorder caused by loss of maternally imprinted genes on 15q11-q13, including melanoma antigen gene family member L2 (MAGEL2). The clinical phenotypes PWS suggest impaired hypothalamic neuroendocrine function; however, the exact cellular defects are unknown. Here, we report deficits in secretory granule (SG) abundance and bioactive neuropeptide production upon MAGEL2 humans mice. Unbiased proteomic analysis Magel2pΔ/m+ mice revealed reduction...