P105 and p100 proteins function as the core of heterogeneous NF-kappaB complexes.

摘要

Biochemistry of the components of signal transduction pathways provides a foundation for the understanding of how cellular signaling events initiate, propagate, and terminate. This thesis describes the multi-protein heterogeneous complexes of NF-kappaB with p105 and p100 proteins. Chapter 1 introduces the NF-kappaB signaling pathway and provides the rational for this thesis research. Chapter 2 describes the results of biochemical characterization of endogenous NF-kappaB and IkappaB proteins that led to the discovery of the high molecular weight heterogeneous complexes of p105 and p100 with other NF-kappaB subunits. Our results show that p105 and p100 complexes function to dynamically sequester newly synthesized p50 and p52 NF-kappaB subunits in macrophages challenged with bacterial lipopolysaccharide. Chapter 3 describes the molecular architecture of p105 and p100 complexes. Experimentally determined composition and biochemical analysis of protein-protein interactions led to the proposal of stoichiometric model for p105 and p100 complexes that accounts for high MW and heterogeneity of these molecular assemblies. Chapter 4 is focused on p105 and p100 proteolysis. p105 and p100 undergo regulated proteolysis that generates p50 and p52 NF-kappaB subunits, respectively. The mechanism of p105 and p100 processing is discussed in the last chapter of this thesis.