Ronald T. Hay
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View article: PML mutants from arsenic-resistant patients reveal SUMO1-TOPORS and SUMO2/3-RNF4 degradation pathways
PML mutants from arsenic-resistant patients reveal SUMO1-TOPORS and SUMO2/3-RNF4 degradation pathways Open
Arsenic effectively treats acute promyelocytic leukemia by inducing SUMO and ubiquitin-dependent degradation of the promyelocytic leukemia (PML)–retinoic acid receptor alpha oncogenic fusion protein. However, some patients relapse with ars…
View article: Mechanism of degrader-targeted protein ubiquitinability
Mechanism of degrader-targeted protein ubiquitinability Open
Small-molecule degraders of disease-driving proteins offer a clinically proven modality with enhanced therapeutic efficacy and potential to tackle previously undrugged targets. Stable and long-lived degrader-mediated ternary complexes driv…
View article: Mechanism of degrader-targeted protein ubiquitinability
Mechanism of degrader-targeted protein ubiquitinability Open
Small molecule degraders of disease-driving proteins offer a clinically proven modality with enhanced therapeutic efficacy and the potential to tackle previously undrugged targets. Thermodynamically stable and kinetically long-lived degrad…
View article: Concerted SUMO-targeted ubiquitin ligase activities of TOPORS and RNF4 are essential for stress management and cell proliferation
Concerted SUMO-targeted ubiquitin ligase activities of TOPORS and RNF4 are essential for stress management and cell proliferation Open
Summary Protein SUMOylation provides a principal driving force for cellular stress responses including DNA-protein crosslink (DPC) repair and arsenic-induced PML body degradation. In genome-scale screens, we identified the human E3 ligase …
View article: Adenovirus E1B-55K controls SUMO-dependent degradation of antiviral cellular restriction factors
Adenovirus E1B-55K controls SUMO-dependent degradation of antiviral cellular restriction factors Open
The human adenovirus species C type 5 (HAdV-C5) early region 1B 55 kDa (E1B-55K) protein is a multifunctional protein that promotes viral replication and adenovirus-mediated cell transformation through various mechanisms that primarily cou…
View article: SUMO protease SENP6 protects the nucleus from hyperSUMOylation-induced laminopathy-like alterations
SUMO protease SENP6 protects the nucleus from hyperSUMOylation-induced laminopathy-like alterations Open
The small ubiquitin-like modifier (SUMO) protease SENP6 disassembles SUMO chains from cellular substrate proteins. We use a proteomic method to identify putative SENP6 substrates based on increased apparent molecular weight after SENP6 dep…
View article: Changes in SUMO-modified proteins in Epstein-Barr virus infection identifies reciprocal regulation of TRIM24/28/33 complexes and the lytic switch BZLF1
Changes in SUMO-modified proteins in Epstein-Barr virus infection identifies reciprocal regulation of TRIM24/28/33 complexes and the lytic switch BZLF1 Open
SUMO modifications regulate the function of many proteins and are important in controlling herpesvirus infections. We performed a site-specific proteomic analysis of SUMO1- and SUMO2-modified proteins in Epstein-Barr virus (EBV) latent and…
View article: Supplementary Figure 1 from Conjugation of Human Topoisomerase 2α with Small Ubiquitin-like Modifiers 2/3 in Response to Topoisomerase Inhibitors: Cell Cycle Stage and Chromosome Domain Specificity
Supplementary Figure 1 from Conjugation of Human Topoisomerase 2α with Small Ubiquitin-like Modifiers 2/3 in Response to Topoisomerase Inhibitors: Cell Cycle Stage and Chromosome Domain Specificity Open
Supplementary Figure 1 from Conjugation of Human Topoisomerase 2α with Small Ubiquitin-like Modifiers 2/3 in Response to Topoisomerase Inhibitors: Cell Cycle Stage and Chromosome Domain Specificity
View article: Data from E3 Ubiquitin Ligase HOIP Attenuates Apoptotic Cell Death Induced by Cisplatin
Data from E3 Ubiquitin Ligase HOIP Attenuates Apoptotic Cell Death Induced by Cisplatin Open
The genotoxin cisplatin is commonly used in chemotherapy to treat solid tumors, yet our understanding of the mechanism underlying the drug response is limited. In a focused siRNA screen, using an siRNA library targeting genes involved in u…
View article: Data from E3 Ubiquitin Ligase HOIP Attenuates Apoptotic Cell Death Induced by Cisplatin
Data from E3 Ubiquitin Ligase HOIP Attenuates Apoptotic Cell Death Induced by Cisplatin Open
The genotoxin cisplatin is commonly used in chemotherapy to treat solid tumors, yet our understanding of the mechanism underlying the drug response is limited. In a focused siRNA screen, using an siRNA library targeting genes involved in u…
View article: Supplementary Figure 1 Legend from Conjugation of Human Topoisomerase 2α with Small Ubiquitin-like Modifiers 2/3 in Response to Topoisomerase Inhibitors: Cell Cycle Stage and Chromosome Domain Specificity
Supplementary Figure 1 Legend from Conjugation of Human Topoisomerase 2α with Small Ubiquitin-like Modifiers 2/3 in Response to Topoisomerase Inhibitors: Cell Cycle Stage and Chromosome Domain Specificity Open
Supplementary Figure 1 Legend from Conjugation of Human Topoisomerase 2α with Small Ubiquitin-like Modifiers 2/3 in Response to Topoisomerase Inhibitors: Cell Cycle Stage and Chromosome Domain Specificity
View article: Data from Conjugation of Human Topoisomerase 2α with Small Ubiquitin-like Modifiers 2/3 in Response to Topoisomerase Inhibitors: Cell Cycle Stage and Chromosome Domain Specificity
Data from Conjugation of Human Topoisomerase 2α with Small Ubiquitin-like Modifiers 2/3 in Response to Topoisomerase Inhibitors: Cell Cycle Stage and Chromosome Domain Specificity Open
Type 2 topoisomerases, in particular the α isoform in human cells, play a key role in cohesion and sister chromatid separation during mitosis. These enzymes are thus vital for cycling cells and are obvious targets in cancer chemotherapy. E…
View article: Supplementary Table 1 from E3 Ubiquitin Ligase HOIP Attenuates Apoptotic Cell Death Induced by Cisplatin
Supplementary Table 1 from E3 Ubiquitin Ligase HOIP Attenuates Apoptotic Cell Death Induced by Cisplatin Open
XLSX file - 196KB, Excel file with siRNA screen data.
View article: Supplementary Figure 1 from Conjugation of Human Topoisomerase 2α with Small Ubiquitin-like Modifiers 2/3 in Response to Topoisomerase Inhibitors: Cell Cycle Stage and Chromosome Domain Specificity
Supplementary Figure 1 from Conjugation of Human Topoisomerase 2α with Small Ubiquitin-like Modifiers 2/3 in Response to Topoisomerase Inhibitors: Cell Cycle Stage and Chromosome Domain Specificity Open
Supplementary Figure 1 from Conjugation of Human Topoisomerase 2α with Small Ubiquitin-like Modifiers 2/3 in Response to Topoisomerase Inhibitors: Cell Cycle Stage and Chromosome Domain Specificity
View article: Supplementary Materials and Methods, Figures 1 - 5 from E3 Ubiquitin Ligase HOIP Attenuates Apoptotic Cell Death Induced by Cisplatin
Supplementary Materials and Methods, Figures 1 - 5 from E3 Ubiquitin Ligase HOIP Attenuates Apoptotic Cell Death Induced by Cisplatin Open
PDF file - 1462KB, Fig. S1: HOIP depletion results in cisplatin hypersensitivity. Fig. S2: HOIP depletion sensitizes cells to genotoxin-induced apoptotic cell death. Fig. S3: HEK293 cells stably expressing HA-IκBα S32A;S36A. Fig. S4: Boxpl…
View article: Data from Conjugation of Human Topoisomerase 2α with Small Ubiquitin-like Modifiers 2/3 in Response to Topoisomerase Inhibitors: Cell Cycle Stage and Chromosome Domain Specificity
Data from Conjugation of Human Topoisomerase 2α with Small Ubiquitin-like Modifiers 2/3 in Response to Topoisomerase Inhibitors: Cell Cycle Stage and Chromosome Domain Specificity Open
Type 2 topoisomerases, in particular the α isoform in human cells, play a key role in cohesion and sister chromatid separation during mitosis. These enzymes are thus vital for cycling cells and are obvious targets in cancer chemotherapy. E…
View article: Supplementary Figure 1 Legend from Conjugation of Human Topoisomerase 2α with Small Ubiquitin-like Modifiers 2/3 in Response to Topoisomerase Inhibitors: Cell Cycle Stage and Chromosome Domain Specificity
Supplementary Figure 1 Legend from Conjugation of Human Topoisomerase 2α with Small Ubiquitin-like Modifiers 2/3 in Response to Topoisomerase Inhibitors: Cell Cycle Stage and Chromosome Domain Specificity Open
Supplementary Figure 1 Legend from Conjugation of Human Topoisomerase 2α with Small Ubiquitin-like Modifiers 2/3 in Response to Topoisomerase Inhibitors: Cell Cycle Stage and Chromosome Domain Specificity
View article: Supplementary Materials and Methods, Figures 1 - 5 from E3 Ubiquitin Ligase HOIP Attenuates Apoptotic Cell Death Induced by Cisplatin
Supplementary Materials and Methods, Figures 1 - 5 from E3 Ubiquitin Ligase HOIP Attenuates Apoptotic Cell Death Induced by Cisplatin Open
PDF file - 1462KB, Fig. S1: HOIP depletion results in cisplatin hypersensitivity. Fig. S2: HOIP depletion sensitizes cells to genotoxin-induced apoptotic cell death. Fig. S3: HEK293 cells stably expressing HA-IκBα S32A;S36A. Fig. S4: Boxpl…
View article: Supplementary Table 1 from E3 Ubiquitin Ligase HOIP Attenuates Apoptotic Cell Death Induced by Cisplatin
Supplementary Table 1 from E3 Ubiquitin Ligase HOIP Attenuates Apoptotic Cell Death Induced by Cisplatin Open
XLSX file - 196KB, Excel file with siRNA screen data.
View article: The p97/VCP segregase is essential for arsenic-induced degradation of PML and PML-RARA
The p97/VCP segregase is essential for arsenic-induced degradation of PML and PML-RARA Open
Acute Promyelocytic Leukemia is caused by expression of the oncogenic Promyelocytic Leukemia (PML)–Retinoic Acid Receptor Alpha (RARA) fusion protein. Therapy with arsenic trioxide results in degradation of PML-RARA and PML and cures the d…
View article: PML mutants resistant to arsenic induced degradation fail to generate the appropriate SUMO and ubiquitin signals required for RNF4 and p97 recruitment
PML mutants resistant to arsenic induced degradation fail to generate the appropriate SUMO and ubiquitin signals required for RNF4 and p97 recruitment Open
Arsenic is an effective treatment for Acute Promyelocytic Leukaemia as it induces degradation of the Promyelocytic Leukaemia (PML) – retinoic acid receptor alpha (RARA) oncogenic fusion protein. Some patients relapse with arsenic resistant…
View article: Identification of an E3 ligase that targets the catalytic subunit of RNA Polymerase I upon transcription stress
Identification of an E3 ligase that targets the catalytic subunit of RNA Polymerase I upon transcription stress Open
RNA Polymerase I (Pol I) synthesizes rRNA, which is the first and rate-limiting step in ribosome biogenesis. Factors governing the stability of the polymerase complex are not known. Previous studies characterizing Pol I inhibitor BMH-21 re…
View article: Negative Modulation of Macroautophagy by Stabilized HERPUD1 is Counteracted by an Increased ER-Lysosomal Network With Impact in Drug-Induced Stress Cell Survival
Negative Modulation of Macroautophagy by Stabilized HERPUD1 is Counteracted by an Increased ER-Lysosomal Network With Impact in Drug-Induced Stress Cell Survival Open
Macroautophagy and the ubiquitin proteasome system work as an interconnected network in the maintenance of cellular homeostasis. Indeed, efficient activation of macroautophagy upon nutritional deprivation is sustained by degradation of pre…
View article: Mechanism and function of DNA replication‐independent DNA‐protein crosslink repair via the SUMO‐RNF4 pathway
Mechanism and function of DNA replication‐independent DNA‐protein crosslink repair via the SUMO‐RNF4 pathway Open
DNA-protein crosslinks (DPCs) obstruct essential DNA transactions, posing a serious threat to genome stability and functionality. DPCs are proteolytically processed in a ubiquitin- and DNA replication-dependent manner by SPRTN and the prot…