Expanding horizons at Big Sky

The Keystone Symposium on Ubiquitin and Signaling took place between 4 and 9 February 2007, in Big Sky, Montana, USA, and was organized by B.A. Schulman, T. Hunter, M.W. Hochstrasser and C.A.P. Joazeiro.![][1] Post‐translational modifications of proteins control a wide range of biological phenomena. An array of inorganic and organic molecules can be covalently attached to proteins, including other proteins such as ubiquitin (Ub) and Ub‐like proteins (Ubls), for example, the small ubiquitin‐like modifier (SUMO) and Nedd8. The covalent attachment of Ub or Ubls to substrate proteins involves a series of transfer reactions that begin with the ATP‐dependent activation of Ub or Ubls by E1, followed by their transfer to E2 and finally their conjugation to substrate proteins, typically onto the ϵ‐amino groups of lysine (Lys) residues. E3 Ub‐ligases are frequently required to trigger conjugation and to confer substrate specificity (Fig 1; Hershko & Ciechanover, 1998). Since its discovery in the 1970s, ubiquitination has been equated with proteasome‐mediated degradation because it is the main regulator of protein abundance in cells. However, other functions of ubiquitination, including protein transport and signalling, are now also well established. More than 25 years of research on ubiquitination has created a detailed understanding of Ub biology. Guided by this knowledge, progress in understanding Ubl modifications has been rapid. Nevertheless, understanding the function of Ubl modifications is still in its infancy and is limited to only a few of the more than ten Ubls that have been identified (Kerscher et al , 2006). What seems to be clear is that most Ubl modifications do not directly induce protein degradation but instead influence signalling functions. This Keystone Symposium on Ubiquitin and Signaling covered many aspects of Ub biology, and the function of SUMO and Nedd8.Figure 1. Ubiquitination. Ubiquitin (Ub) is activated by E1, transferred to E2s, which bind … [1]: /embed/graphic-1.gif