CHAPTER 8 FUNCTIONS OF LINEAR UBIQUITIN CHAINS IN THE NF-kappaB PATHWAY Linear Polyubiquitin in NF-kappaB Signaling

摘要

The ubiquitin conjugation system regulates a wide variety of biological phenomena, inmostcases, bymodulatingprotein function viapolyubiquitin conjugation. Several types of polyubiquitin chains exist in cells and the type of chain conjugated to a protein seems to determine how the protein is regulated. The polyubiquitin chains that have been reported thus far are generated by conjugation via Lys residues of ubiquitin. We have identified a novel linear polyubiquitin chain, in which the C-terminal Gly of one ubiquitin is conjugated to the alpha-amino group of the N-terminal Met of another ubiquitin and the ubiquitin ligase complex mediating these reactions specifically generates linear chains. We have shown that linear polyubiquitination is involved in activation of the canonical NF-kappaB pathway. The regulatory roles of Lys63-linkedubiquitin chains in the NF-kappaB pathway have been extensively studied. In this chapter, we will discuss the distinct roles of linear and K63-linked ubiquitin chains in TNF-alpha mediated NF-kappaB activation and the future directions for linear ubiquitin chain research.