VHL substrate transcription factor ZHX2 as an oncogenic driver in clear cell renal cell carcinoma

Inactivation of the von Hippel-Lindau (VHL) E3 ubiquitin ligase protein is a hallmark of clear cell renal cell carcinoma (ccRCC). Identifying how pathways affected by VHL loss contribute to ccRCC remains challenging. We used a genome-wide in vitro expression strategy to identify proteins that bind VHL when hydroxylated. Zinc fingers and homeoboxes 2 (ZHX2) was found as a VHL target, and its hydroxylation allowed VHL to regulate its protein stability. Tumor cells from ccRCC patients with VHL loss-of-function mutations usually had increased abundance and nuclear localization of ZHX2. Functionally, depletion of ZHX2 inhibited VHL-deficient ccRCC cell growth in vitro and in vivo. Mechanistically, integrated chromatin immunoprecipitation sequencing and microarray analysis showed that ZHX2 promoted nuclear factor B activation. These studies reveal ZHX2 as a potential therapeutic target for ccRCC.
Source: ScienceNOW - Category: Science Authors: Tags: Cell Biology, Medicine, Diseases reports Source Type: news

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Series Type : Expression profiling by array ; Genome binding/occupancy profiling by high throughput sequencing ; Expression profiling by high throughput sequencingOrganism : Homo sapiens ; Mus musculusThis SuperSeries is composed of the SubSeries listed below.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Genome binding/occupancy profiling by high throughput sequencing Expression profiling by high throughput sequencing Homo sapiens Mus musculus Source Type: research
Contributors : David Schoenfeld ; Sakellarios Zairis ; William Su ; Nicole Steinbach ; Dan Hasson ; Deepti Mathur ; Asif Chowdhury ; Bertilia Tavarez ; Emily Bernstein ; Raul Rabadan ; Ramon ParsonsSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensSubunits of SWI/SNF chromatin remodeling complexes are frequently mutated in human malignancies. The PBAF complex is composed of multiple subunits, including the putative tumor suppressor proteins PBRM1 (BAF180) and ARID2 (BAF200) that are unique to this SWI/SNF complex. PBRM1 is mutated in various cancers, with a high mutation frequency in cl...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Contributors : David Schoenfeld ; Sakellarios Zairis ; William Su ; Nicole Steinbach ; Dan Hasson ; Deepti Mathur ; Asif Chowdhury ; Bertilia Tavarez ; Emily Bernstein ; Raul Rabadan ; Ramon ParsonsSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensSubunits of SWI/SNF chromatin remodeling complexes are frequently mutated in human malignancies. The PBAF complex is composed of multiple subunits, including the putative tumor suppressor proteins PBRM1 (BAF180) and ARID2 (BAF200) that are unique to this SWI/SNF complex. PBRM1 is mutated in various cancers, with a high mutation f...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research
Contributors : David Schoenfeld ; Sakellarios Zairis ; William Su ; Nicole Steinbach ; Dan Hasson ; Deepti Mathur ; Asif Chowdhury ; Bertilia Tavarez ; Emily Bernstein ; Raul Rabadan ; Ramon ParsonsSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensSubunits of SWI/SNF chromatin remodeling complexes are frequently mutated in human malignancies. The PBAF complex is composed of multiple subunits, including the putative tumor suppressor proteins PBRM1 (BAF180) and ARID2 (BAF200) that are unique to this SWI/SNF complex. PBRM1 is mutated in various cancers, with a high mutation f...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research
Contributors : David Schoenfeld ; Sakellarios Zairis ; William Su ; Nicole Steinbach ; Dan Hasson ; Deepti Mathur ; Asif Chowdhury ; Bertilia Tavarez ; Emily Bernstein ; Raul Rabadan ; Ramon ParsonsSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensSubunits of SWI/SNF chromatin remodeling complexes are frequently mutated in human malignancies. The PBAF complex is composed of multiple subunits, including the putative tumor suppressor proteins PBRM1 (BAF180) and ARID2 (BAF200) that are unique to this SWI/SNF complex. PBRM1 is mutated in various cancers, with a high mutation f...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research
Contributors : David Schoenfeld ; Sakellarios Zairis ; William Su ; Nicole Steinbach ; Dan Hasson ; Deepti Mathur ; Asif Chowdhury ; Bertilia Tavarez ; Emily Bernstein ; Raul Rabadan ; Ramon ParsonsSeries Type : Expression profiling by arrayOrganism : Mus musculusSubunits of SWI/SNF chromatin remodeling complexes are frequently mutated in human malignancies. The PBAF complex is composed of multiple subunits, including the putative tumor suppressor proteins PBRM1 (BAF180) and ARID2 (BAF200) that are unique to this SWI/SNF complex. PBRM1 is mutated in various cancers, with a high mutation frequency in clear cell renal cell c...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Mus musculus Source Type: research
Cell Proliferation, EarlyView.
Source: Cell Proliferation - Category: Cytology Authors: Source Type: research
Dr. Daniel Goldstein discusses the results of a trial of first line pembrolizumab (Keytruda) as first line therapy for patients with metastatic clear cell renal cell carcinoma and the implications for... Author: BeaconMedIC Added: 08/12/2018
Source: Oncology Tube - Category: Cancer & Oncology Source Type: podcasts
AbstractPurpose of ReviewTo review the growth kinetics of small renal masses and available imaging modalities for mass characterization and surveillance, highlight current organizational recommendations for the active surveillance of small renal masses, and discuss the most recently reported oncological outcomes of patients as they relate to various surveillance imaging protocols and progression to delayed intervention.Recent FindingsOverall, organizational guideline recommendations are broad and lack specifics regarding timing and modality for follow-up imaging of small renal masses. Additionally, despite general consensu...
Source: Current Urology Reports - Category: Urology & Nephrology Source Type: research
We report that the disruption of excitation-contraction coupling contributes to impaired force generation in the mouse model of Sod1 deficiency. Briefly, we found a significant reduction in sarcoplasmic reticulum Ca2+ ATPase (SERCA) activity as well as reduced expression of proteins involved in calcium release and force generation. Another potential factor involved in EC uncoupling in Sod1-/- mice is oxidative damage to proteins involved in the contractile response. In summary, this study provides strong support for the coupling between increased oxidative stress and disruption of cellular excitation contraction mac...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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