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The role of ubiquitination

The role of ubiquitination in VHL function

Under normoxic conditions, HIF-1α is marked for degradation through a process known as ubiquitination. In ubiquitination, molecular tags, or ubiquitins, are added to HIF-1α, signaling that HIF-1α is to be destroyed through proteasome degradation. Dysregulation of the ubiquitination process causes HIF-1α to accumulate in the cell and induce expression of a number of gene products, including VEGF.¹

George DJ, Kaelin WG Jr. N Engl J Med. 2003;349:419-421. Copyright © 2003 Massachusetts Medical Society.

Ubiquitination is a cellular regulatory process in which proteins called ubiquitins are added to another, larger protein—the target protein. This process acts as a signal for the target protein to undergo degradation. Under normoxic conditions and with normal von Hippel-Lindau gene (VHL) function, the VHL protein (pVHL) plays a role in the ubiquitination and subsequent degradation of hypoxia-inducible factor-1α (HIF-1α).^1-3

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References:

1.

George DJ, Kaelin WG Jr. N Engl J Med. 2003;349:419-421.

2.

Haase VH. Kidney Int. 2006;69:1302-1307.

3.

Huang LE, Gu J, Schau M, Bunn HF. Proc Natl Acad Sci USA. 1998;95:7987-7992.