A5047952875- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- DNA Repair Mechanisms
- Prostate Cancer Treatment and Research
- RNA modifications and cancer
- Genetic Mapping and Diversity in Plants and Animals
- Evolution and Genetic Dynamics
- Insect-Plant Interactions and Control
- Histone Deacetylase Inhibitors Research
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Enzyme Structure and Function
- Biomedical Ethics and Regulation
- Pluripotent Stem Cells Research
- Heat shock proteins research
- Plant Virus Research Studies
- Gene Regulatory Network Analysis
- Plant Disease Resistance and Genetics
- Autophagy in Disease and Therapy
- Plant Genetic and Mutation Studies
- Cancer, Hypoxia, and Metabolism
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- PARP inhibition in cancer therapy
Rutgers, The State University of New Jersey
2022-2025
Johnson University
2022-2025
Sidney Kimmel Cancer Center
2009-2023
Rutgers Sexual and Reproductive Health and Rights
2022
Thomas Jefferson University
2009-2021
Tampere University Hospital
2013
Johns Hopkins University
2013
Sidney Kimmel Comprehensive Cancer Center
2013
Tampere University
2013
Abstract Increasing evidence links deregulation of the ubiquitin-specific proteases 22 (USP22) deubitiquitylase to cancer development and progression in a select group tumor types, but its specificity underlying mechanisms action are not well defined. Here we show that USP22 is critical promoter lethal phenotypes acts by modulating nuclear receptor oncogenic signaling. In multiple xenograft models human cancer, modeling tumor-associated demonstrated controls androgen accumulation signaling,...
Significance The deubiquitylase USP22 is frequently overexpressed in cancer and contributes to tumorigenesis by driving cell cycle progression. Current models define as functional mediator of gene regulation chromatin modification, working within the SAGA transcriptional cofactor complex. Here we report a catalytic role for distinct from its well-characterized transcription regulatory capacity. directly stabilizes essential G1-cyclin, CCND1, protecting it proteasome-mediated degradation via...
Chromosomal instability (CIN) in tumors is characterized by chromosomal abnormalities and an altered gene expression signature; however, the mechanism of CIN poorly understood. CCND1 (which encodes cyclin D1) overexpressed human malignancies has been shown to play a direct role transcriptional regulation. Here, we used genome-wide ChIP sequencing found that DNA-bound form D1 occupied regulatory region genes governing integrity mitochondrial biogenesis. Adding back Ccnd1–/– mouse embryonic...
Emerging evidence indicates the deubiquitinase USP22 regulates transcriptional activation and modification of target substrates to promote pro-oncogenic phenotypes. Here,
The tumor suppressor p53 induces apoptosis by altering the transcription of pro-apoptotic targets in nucleus and a direct, nontranscriptional role at mitochondria. Although post-translational modifications regulating nuclear apoptotic functions have been thoroughly characterized, little is known how transcription-independent are controlled. We others identified acetylation DNA binding domain lysine 120 as critical event induction. initial studies showed that Lys-120 plays function nucleus,...
Aberrant activation of transposable elements (TEs) has been a well-documented source genomic instability and disease, stemming from their insertion into genes imposition epigenetic effects on nearby loci. However, the extent to which disruptive involve concomitant or subsequent formation DNA:RNA hybrids (R-loops) remains unknown. Here we used immunoprecipitation followed by high-throughput sequencing (DRIP-seq) map R-loop profiles TEs satellites in D. melanogaster ovaries control rhino...
In unstressed cells, the p53 tumor suppressor is highly unstable. DNA damage and other forms of cellular stress rapidly stabilize activate p53. This process regulated by a complex array post-translational modifications that are dynamically deposited onto Recent studies show these orchestrate p53-mediated processes such as cell cycle arrest apoptosis. Cancer cells carry inherent genetic damage, but avoid apoptosis inactivating Defining enzymatic machinery regulates stress-induced modification...
Aberrant MYC expression is a common oncogenic event in human cancer. Paradoxically, can either drive cell cycle progression or induce apoptosis. The latent ability of to apoptosis has been termed "intrinsic tumor suppressor activity," and reactivating this apoptotic function tumors widely considered valuable therapeutic goal. As transcription factor, controls the many downstream targets, for majority these, it remains unclear whether not they play direct roles function. To identify subset...
Article22 June 2021Open Access Source DataTransparent process The SAGA complex regulates early steps in transcription via its deubiquitylase module subunit USP22 Timothy J Stanek orcid.org/0000-0001-9192-4978 Department of Biochemistry and Molecular Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA Search for more papers by this author Victoria Gennaro Mason A Tracewell Daniela Di Marcantonio Blood Cell Development Function Program, Fox Chase Cancer...
R-loops are three-stranded nucleotide structures consisting of a DNA:RNA hybrid and displaced ssDNA non-template strand. Previous work suggests that R-loop formation is primarily determined by the thermodynamics binding, which governed base composition (e.g., GC skew) transcription-induced DNA superhelicity. However, have been described at genomic locations lack these properties, suggesting they may serve other context-specific roles. To better understand genetic determinants formation, we...
During the processing of this manuscript, Western blot in Figure 3D
Gene model for the ortholog of
<div>Abstract<p>Emerging evidence indicates the deubiquitinase USP22 regulates transcriptional activation and modification of target substrates to promote pro-oncogenic phenotypes. Here, <i>in vivo</i> characterization tumor-associated upregulation unbiased interrogation USP22-regulated functions vitro</i> demonstrated critical roles for in prostate cancer. Specifically, clinical datasets validated that expression is elevated cancer, a novel murine model...
<div>Abstract<p>Emerging evidence indicates the deubiquitinase USP22 regulates transcriptional activation and modification of target substrates to promote pro-oncogenic phenotypes. Here, <i>in vivo</i> characterization tumor-associated upregulation unbiased interrogation USP22-regulated functions vitro</i> demonstrated critical roles for in prostate cancer. Specifically, clinical datasets validated that expression is elevated cancer, a novel murine model...
<p>PDF file - 176K, Supplementary Figure S1: USP22 Specifically Promotes AR Recruitment to Target Loci. 2: Depletion of can be mediated by multiple sequences.Supplementary S3: Ubiquitylation Levels are not Altered in Response Depletion.</p>
<p>PDF file - 176K, Supplementary Figure S1: USP22 Specifically Promotes AR Recruitment to Target Loci. 2: Depletion of can be mediated by multiple sequences.Supplementary S3: Ubiquitylation Levels are not Altered in Response Depletion.</p>
<p>SF1: Analysis of USP22 expression with known drivers disease progression; SF2: modulates DNA repair factors and survival after damage; SF3: Genetically engineered mouse model tumor-associated expression; SF4: The USP22-sensitive ubiquitylome reveals altered modification proteins; SF5: deubiquitylates the NER protein XPC, modulating foci formation.</p>
<p>SF1: Analysis of USP22 expression with known drivers disease progression; SF2: modulates DNA repair factors and survival after damage; SF3: Genetically engineered mouse model tumor-associated expression; SF4: The USP22-sensitive ubiquitylome reveals altered modification proteins; SF5: deubiquitylates the NER protein XPC, modulating foci formation.</p>
<div>Abstract<p>Increasing evidence links deregulation of the ubiquitin-specific proteases 22 (USP22) deubitiquitylase to cancer development and progression in a select group tumor types, but its specificity underlying mechanisms action are not well defined. Here we show that USP22 is critical promoter lethal phenotypes acts by modulating nuclear receptor oncogenic signaling. In multiple xenograft models human cancer, modeling tumor-associated demonstrated controls androgen...
<div>Abstract<p>Increasing evidence links deregulation of the ubiquitin-specific proteases 22 (USP22) deubitiquitylase to cancer development and progression in a select group tumor types, but its specificity underlying mechanisms action are not well defined. Here we show that USP22 is critical promoter lethal phenotypes acts by modulating nuclear receptor oncogenic signaling. In multiple xenograft models human cancer, modeling tumor-associated demonstrated controls androgen...