Processing of NF-kappa B2 precursor protein p100 to generate p52 is tightly 
regulated. However, this proteolytic event could be actively induced by the 
NF-kappa B-inducing kinase and the human T-cell leukemia virus-encoded 
oncoprotein Tax or be constitutively turned on due to the loss of the C-terminal 
portion of p100. Whereas NF-kappa B-inducing kinase-mediated p100 processing 
requires beta-transducin repeat-containing protein, constitutive processing of 
p100 is independent of this protein. On the other hand, Tax-induced processing 
of p100 appears to be both beta-transducin repeat-containing protein-dependent 
and -independent. We show here that, besides the C-terminal sequences, multiple 
functional regions, including the two alpha-helices, dimerization domain, 
nuclear localization sequence, and glycine-rich region, located in the N 
terminus of p100, also play important roles in both constitutive and inducible 
processing, suggesting a common mechanism for p100 processing. We further 
demonstrate that with the help of the C-terminal death domain and I kappa B 
kinase alpha-targeting serines, the C-terminal ankyrin-repeat domain of p100 
strongly interacts with its N-terminal dimerization domain and nuclear 
localization sequence, thereby bringing the C- and N-terminal sequences together 
to form a three-dimensional domain. This presumptive domain is not only 
responsible for suppression of constitutive processing but also required for 
inducible processing of p100. Taken together, these studies highlight the 
mechanism by which the different sequences within p100 work in concert to 
regulate its processing and shed light on the mechanisms of how p100 processing 
is tightly and delicately controlled.