Final answer:
Mutations in the VHL gene are associated with several types of cancer, including renal cell carcinoma and pheochromocytoma, and can lead to non-functional HIF regulation. The p53 gene, a tumor suppressor functioning as a transcription factor, is frequently mutated in cancers and is associated with Li-Fraumeni syndrome, resulting in a high cancer risk.
Step-by-step explanation:
Loss of function mutations in the VHL gene are linked to not only renal cell cancers and pheochromocytoma but also to other potential cancers such as melanoma, non-small cell lung cancer, Hodgkin lymphoma, and bladder cancer. The transcription factor critical for VHL ubiquitin ligase activity is hypoxia-inducible factor (HIF),
which is targeted for degradation by the VHL protein in normal oxygen conditions. When VHL is non-functional due to a mutation, HIF is not properly degraded, leading to the activation of genes that contribute to cancerous growth, such as those involved in angiogenesis and cell proliferation.
The role of tumor suppressor genes such as p53 is essential in regulating cell proliferation and preventing cancer development. p53 functions as a transcription factor and is mutated in over 50 percent of all cancer types.
A mutation in p53, such as seen in Li-Fraumeni syndrome (LFS1), dramatically alters the transcriptional activity of its target genes, contributing to unchecked cell cycle progression and cancer development.