Transcriptional control of kidney cancer

• Published in: Science (American Association for the Advancement of Science) 2018-07, Vol.361 (6399), p.226-227
• Main Authors: Sanchez, Danielle J, Simon, M Celeste
• Format: Article
• Language: English
• Subjects: Angiogenesis; Cancer; Clear cell-type renal cell carcinoma; Deactivation; Degradation; Gene Expression Regulation; Humans; Hypoxia; Hypoxia-inducible factors; Inactivation; Kidney; Kidney cancer; Kidney Neoplasms; Kidneys; Metabolism; Neoplasia; NF-κB protein; Proteasomes; Proteins; Substrates; Transcription factors; Transcription, Genetic; Tumorigenesis; VHL protein; Zinc; Zinc finger proteins
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.aau4385

Stabilization of the transcription factor ZHX2 promotes kidney tumor growth Clear cell renal cell carcinoma (ccRCC) is a subtype of kidney cancer characterized by inactivation of the von Hippel-Lindau ( VHL ) gene in ∼90% of patients. VHL is the substrate recognition component of an E3 ubiqutin ligase complex that targets prolyl-hydroxylated proteins for proteasomal degradation ( 1 ). The canonical targets of VHL are the α subunits of hypoxia-inducible factors (HIFs), which are oxygen-labile transcription factors that become constitutively stabilized early in ccRCC development and consequently direct transcriptional programs that promote angiogenesis and rewiring of intracellular metabolism ( 2 – 4 ). Identifying VHL substrates other than HIFαs that escape degradation and contribute to tumorigenesis could represent a new therapeutic approach for ccRCC. On page 290 of this issue, Zhang et al. ( 5 ) demonstrate that the transcription factor zinc fingers and homeoboxes 2 (ZHX2) is a previously unidentified VHL target that promotes ccRCC tumorigenesis through regulation of nuclear factor κB (NF-κB) signaling, potentially identifying targets to treat ccRCC.