A switch in distinct I kappa B alpha degradation mechanisms mediates constitutive NF-kappa B activation in mature B cells.
Inducible activation of cytoplasmic NF-kappa B/Rel transcription factors occurs via proteasome-dependent degradation of an associated inhibitor, termed I kappa B alpha. Mature B lymphocytes constitutively express nuclear NF-kappa B, which is important for their long-term survival. The intrinsic mechanisms by which B cells constitutively activate NF-kappa B are unknown. In this paper we demonstrate that maintenance of NF-kappa B activity in primary B cells is mediated by a novel calcium-dependent, but proteasome-independent, mechanism. Moreover, we show that differentiation of conditionally transformed pre-B cells is accompanied by a switch from proteasome-dependent to proteasome-independent degradation of I kappa B alpha. Our findings indicate that I kappa B alpha degradation mechanisms are dynamic during B cell development, and ultimately establish constitutive NF-kappa B activity in mature B lymphocytes.
Fields
E R
ER
Department of Pharmacology, University of Wisconsin Medical School, Madison, WI 53792, USA.
Seufzer
B J
BJ
Oltz
E M
EM
Miyamoto
S
S
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D002118:Calcium / Q000502:physiology; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D020672:I-kappa B Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009097:Multienzyme Complexes / Q000502:physiology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016374:Oncogene Proteins v-abl / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D013154:Spleen / Q000166:cytology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013696:Temperature
D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D009097:Multienzyme Complexes; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D016374:Oncogene Proteins v-abl; D000072000:NF-KappaB Inhibitor alpha; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D002118:Calcium