Oral Presentation 6th Australian Health and Medical Research Congress 2012

Nedd4 family of ubiquitin ligases in physiology and disease (#231)

Sharad Kumar 1
  1. Centre for Cancer Biology & UniSA, Adelaide, SA, Australia

Protein modification by ubiquination controls a number of cellular processes, including protein trafficking and turnover. Ubiquitination is mediated via a number of enzymes that include a ubiquitin activating enzyme (E1), ubiquitin conjugating enzymes (E2s) and ubiquitin ligases (E3s). The specificity of the ubiquitination system is determined by E3s, as they are involved in the transfer of ubiquitin from an E2 to a specific substrate. The two main types of E3s include the RING E3s, that mostly act as a large complex, and the HECT E3s, which are single chain enzymes that first accept ubiquitin and then transfer it to the substrate. Among HECT ligases, the members of Nedd4 family are characterized by a unique modular domain architecture containing a C2 domain, 2-4 WW domains and a Cterminal HECT domain (reviewed in 1). Many members of this family are involved in the control of trafficking and endocytosis of membrane associated proteins, including ion channels, transporters and receptors. We are studying the physiological functions of several members of the Nedd4 family using biochemical, cellular, physiological and gene knockout approaches. I will discuss some of our recent work on these important E3s and their potential roles in disease, with a focus on Nedd4-2, that is a critical regulator of sodium homeostasis.

  1. Rotin D, Kumar S (2009) Physiological functions of the HECT family of ubiquitin ligases. Nature Reviews | Mol. Cell Biol. 10: 398-409.