scholarly journals E3 Ubiquitin Ligase Von Hippel–Lindau Protein Promotes Th17 Differentiation

2020 ◽  
Vol 205 (4) ◽  
pp. 1009-1023
Author(s):  
Alisha Chitrakar ◽  
Scott A. Budda ◽  
Jacob G. Henderson ◽  
Robert C. Axtell ◽  
Lauren A. Zenewicz
Keyword(s):  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Von Hippel Lindau ◽  
Th17 Differentiation

scholarly journals Therapeutically actionable signaling node to rescue AURKA driven loss of primary cilia in VHL-deficient cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pratim Chowdhury ◽  
Dimuthu Perera ◽  
Reid T. Powell ◽  
Tia Talley ◽  
Durga Nand Tripathi ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Primary Cilia ◽  
Mtor Inhibitor ◽  
E3 Ubiquitin Ligase ◽  
Xenograft Model ◽  
Aurora Kinase ◽  
Tumor Burden ◽  
Aurora Kinase A ◽  
Von Hippel Lindau ◽  
In Cells

AbstractLoss of primary cilia in cells deficient for the tumor suppressor von Hippel Lindau (VHL) arise from elevated Aurora Kinase A (AURKA) levels. VHL in its role as an E3 ubiquitin ligase targets AURKA for degradation and in the absence of VHL, high levels of AURKA result in destabilization of the primary cilium. We identified NVP-BEZ235, a dual PI3K/AKT and mTOR inhibitor, in an image-based high throughput screen, as a small molecule that restored primary cilia in VHL-deficient cells. We identified the ability of AKT to modulate AURKA expression at the transcript and protein level. Independent modulation of AKT and mTOR signaling decreased AURKA expression in cells confirming AURKA as a new signaling node downstream of the PI3K cascade. Corroborating these data, a genetic knockdown of AKT in cells deficient for VHL rescued the ability of these cells to ciliate. Finally, inhibition of AKT/mTOR using NVP-BEZ235 was efficacious in reducing tumor burden in a 786-0 xenograft model of renal cell carcinoma. These data highlight a previously unappreciated signaling node downstream of the AKT/mTOR pathway via AURKA that can be targeted in VHL-null cells to restore ciliogenesis.

scholarly journals The von Hippel–Lindau Cullin-RING E3 ubiquitin ligase regulates APOBEC3 cytidine deaminases

2021 ◽  
Author(s):  
Gaël K. Scholtès ◽  
Aubrey M. Sawyer ◽  
Cristina C. Vaca ◽  
Isabelle Clerc ◽  
Meejeon Roh ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Cytidine Deaminases ◽  
Von Hippel Lindau ◽  
Ring E3

scholarly journals Development of Selective Histone Deacetylase 6 (HDAC6) Degraders Recruiting Von Hippel–Lindau (VHL) E3 Ubiquitin Ligase

2020 ◽  
Vol 11 (4) ◽  
pp. 575-581 ◽  
Author(s):  
Ka Yang ◽  
Hao Wu ◽  
Zhongrui Zhang ◽  
Eric D. Leisten ◽  
Xueqing Nie ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Histone Deacetylase 6 ◽  
Von Hippel Lindau

scholarly journals Playing Tag with HIF: The VHL Story

2002 ◽  
Vol 2 (3) ◽  
pp. 131-135 ◽  
Author(s):  
Sherri K. Leung ◽  
Michael Ohh
Keyword(s):  
Ubiquitin Ligase ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Hypoxia Inducible Factor ◽  
E3 Ubiquitin Ligase ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Matrix Assembly ◽  
Von Hippel Lindau ◽  
Ubiquitin Ligase Complex

Inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene product pVHL is the cause of inherited VHL disease and is associated with sporadic kidney cancer. pVHL is found in a multiprotein complex with elongins B/C, Cul2, and Rbx1 forming an E3 ubiquitin ligase complex called VEC. This modular enzyme targets theαsubunits of hypoxia-inducible factor (HIF) for ubiquitin-mediated destruction. Consequently, tumour cells lacking functional pVHL overproduce the products of HIF-target genes such as vascular endothelial growth factor (VEGF), which promotes angiogenesis. This likely accounts for the hypervascular nature of VHL-associated neoplasms. Although pVHL has been linked to the cell-cycle, differentiation, and the regulation of extracellular matrix assembly, microenvironment pH, and tissue invasiveness, this review will focus on the recent insights into the molecular mechanisms governing the E3 ubiquitin ligase function of VEC.

scholarly journals Multiple Splice Variants of the Human HIF-3α Locus Are Targets of the von Hippel-Lindau E3 Ubiquitin Ligase Complex

2003 ◽  
Vol 278 (13) ◽  
pp. 11032-11040 ◽  
Author(s):  
Mindy A. Maynard ◽  
Heng Qi ◽  
Jacky Chung ◽  
Eric H. L. Lee ◽  
Yukihiro Kondo ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Splice Variants ◽  
E3 Ubiquitin Ligase ◽  
Von Hippel Lindau ◽  
Ubiquitin Ligase Complex

scholarly journals The E3 Ubiquitin Ligase Adaptor Ndfip1 Regulates Th17 Differentiation by Limiting the Production of Proinflammatory Cytokines

2012 ◽  
Vol 188 (8) ◽  
pp. 4023-4031 ◽  
Author(s):  
Hilda E. Ramon ◽  
Allison M. Beal ◽  
Yuhong Liu ◽  
George Scott Worthen ◽  
Paula M. Oliver
Keyword(s):  
Ubiquitin Ligase ◽  
Proinflammatory Cytokines ◽  
E3 Ubiquitin Ligase ◽  
Th17 Differentiation
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