TBK1 Activation by VHL Loss in Renal Cell Carcinoma: A Novel HIF-Independent Vulnerability
Ziad Bakouny, David A. Barbie
Abstract
Abstract Summary: The Von Hippel-Lindau gene product is a tumor suppressor whose ubiquitin ligase function is key to oxygen-sensing in cells, whereas Tank-binding kinase (TBK1) is a kinase mostly implicated in innate immune response. The study by Hu and colleagues in this issue reveals that VHL suppresses TBK1 activity under normoxic conditions, and that loss of VHL in kidney cancer cells renders them sensitive to TBK1 inhibition, providing a new potential target for the treatment of clear cell renal cell carcinoma. See related article by Hu et al., p. 460.
Topics & Concepts
Ubiquitin ligaseCancer researchUbiquitinTANK-binding kinase 1SuppressorRenal cell carcinomaKidney cancerBiologyKidneyTumor suppressor geneKinaseCancerMedicineCell biologyGeneInternal medicineProtein kinase ACarcinogenesisEndocrinologyGeneticsMAP kinase kinase kinaseCancer, Hypoxia, and MetabolismAutophagy in Disease and TherapyUbiquitin and proteasome pathways