Cell Biology MCAT Practice Question
A 54-year-old man with a history of renal cell carcinoma undergoes tumor genomic sequencing. Analysis reveals a loss-of-function mutation in the VHL gene (von Hippel-Lindau). Immunohistochemistry shows persistently elevated HIF-1α (hypoxia-inducible factor 1-alpha) protein within the tumor cells despite adequate tissue oxygenation. Further biochemical analysis demonstrates that HIF-1α protein undergoes normal ubiquitination in vitro when synthetic hydroxylated HIF-1α peptides are incubated with VHL and ubiquitin-conjugating enzymes. However, endogenous HIF-1α in the tumor cells is not ubiquitinated despite VHL mutation alone. Which of the following enzymatic modifications of HIF-1α is most likely impaired in these cancer cells?
Answer choices
- APhosphorylation of serine residues by GSK-3β kinase
- BHydroxylation of proline residues by prolyl hydroxylase (PHD2)Correct answer
- CAcetylation of lysine residues by p300 histone acetyltransferase
- DSumoylation of lysine residues by SUMO E3 ligase
- ENeddylation of lysine residues by NEDD8 E3 ligase
- FMethylation of arginine residues by protein methyltransferase
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