Here, the tumor suppressor GSK3β phosphorylates HIF-1α at three serine residues within the human HIF-1α N-terminal transactivation domain (21, 22), which results in the Fbw7 and USP28-mediated HIF-1α ubiquitination and VHL-independent proteasomal degradation (23). The gene discussed is VHL; the disease is neoplasm.