Supplementary Tables 1 - 7 and Figures 1 - 3 from Genetic Evidence of a Precisely Tuned Dysregulation in the Hypoxia Signaling Pathway during Oncogenesis
Year: 2023
Type: supplementary-materials
Abstract: Table S1: Phenotypes associated with single R161Q and R200W VHL germline mutations are different from the phenotype associated with the combined mutations. Table S2: VHL mutations associated with polycythemia are different from the VHL mutations involved in severe von Hippel-Lindau disease. Table S3: Members of the family carrying the VHL-R200W+R161Q mutations present normal hematological values. Table S4: Intra-domain hydrogen bonds are severely destabilized by the mutations. Table S5: The double mutant reduced the inter-domain mobility compared to the single one. Table S6: The pVHL/HIF-2α direct target genes are deregulated with a significantly ascending gradient by the pVHL mutants of increased severity. Table S7: The target genes of the pVHL/HIF-2α axis that are deregulated in renal cell carcinoma play a role in oncogenic pathways. Figure S1: Germline mutations in the VHL gene are associated with distinct phenotypes. Figure S2: (A) The crystallographic structure of pVHL contains a seven-stranded β-sandwich connected to four α-helices by a flexible linker. (B) The R200W mutation dramatically weakens hydrogen bonds established in the wild-type form between Arg200 and Glu134, and between Arg197 and Arg120. (C) The R161Q mutation indirectly influences crucial stabilizing interactions involving primarily Arg 167. Figure S3: VHL mRNA expression is equivalent in 786.O cells transduced by the different VHL inducible lentiviral constructs.
Authors: Sophie Couvé, Charline Ladroue, Elodie Laine, Karène Mahtouk, Justine Guégan, Sophie Gad, Hélène Le Jeune, Marion Le Gentil, Gregory Nuel, William Y. Kim, Bernard Lecomte, Jean-Christophe Pagès, Christine Collin, Françoise Lasne, Patrick R. Benusiglio, Brigitte Bressac-de Paillerets, Jean Feunteun, Vladimir Lazar, Anne-Paule Gimenez-Roqueplo, Nathalie M. Mazure, Philippe Dessen, Luba Tchertanov, David R. Mole, William Kaelin, Peter Ratcliffe, Stéphane Richard, Betty Gardie
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4362242456