At the crossroads of SUMO and NF-kappaB.
BACKGROUND
Recognition of pathogens by immune receptors leads to activation of macrophages, dendritic cells, and lymphocytes. Signals are communicated to enhance expression of target molecules such as cytokines and adhesion molecules, depending on activation of various inducible transcription factors, among which the family NF-kappaB transcription factors plays an evolutionarily conserved and critical role. Classical activation of NF-kappaB involves phosphorylation, polyubiquitination and subsequent degradation of the inhibitor molecules of NF-kappaB, referred to as IkappaB. Modification of IkappaBalpha, one of the mammalian IkappaB isoforms, with the small ubiquitin-like modifier (SUMO) results its protection from degradation.


OBJECTIVE
SUMO-IkappaBalpha localizes in the nucleus. The nuclear SUMO-IkappaBalpha pool may be dynamic. SUMO-IkappaBalpha functions as synergy control factor.


METHODS
Immunoprecipitation from cellular fractions, 35S methionine pulse-chase, and FRET assays should reveal the localization of SUMO-IkappaBalpha and the dynamics of the pool. Expression of SUMOylation defective IkappaBalpha in an IkappaBalpha -/- background should yield insights into the function of SUMO-IkappaBalpha.


CONCLUSIONS
IkappaBalpha contains the required SUMOylation motif but IkappaBbeta does not. The suggested study would provide evidence whether or not IkappaBalpha and IkappaBbeta can substitute each other. In addition, the suggested assays would reveal a possible redundancy in controlling transcriptional activity of NF-kappaB.
Kracklauer
Martin P
MP
Section of Molecular Cell and Developmental Biology, Institute for Cellular and Molecular Biology, The University of Texas at Austin, 1 University Station, A4800, Austin, TX 78712, USA. mordechai30@hotmail.com
Schmidt
Christian
C
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D008954:Models, Biological; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000378:metabolism*
C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D025842:SUMO-1 Protein; D000072000:NF-KappaB Inhibitor alpha