Defective lymphotoxin-β receptor-induced NF-κB transcriptional activity in NIK-deficient mice

L Yin, L Wu, H Wesche, CD Arthur, JM White… - Science, 2001 - science.org
L Yin, L Wu, H Wesche, CD Arthur, JM White, DV Goeddel, RD Schreiber
Science, 2001science.org
The role of NF-κB–inducing kinase (NIK) in cytokine signaling remains controversial. To
identify the physiologic functions of NIK, we disrupted the NIK locus by gene targeting.
Although NIK–/–mice displayed abnormalities in both lymphoid tissue development and
antibody responses, NIK–/–cells manifested normal NF-κB DNA binding activity when
treated with a variety of cytokines, including tumor necrosis factor (TNF), interleukin-1 (IL-1),
and lymphotoxin-β (LTβ). However, NIK was selectively required for gene transcription …
The role of NF-κB–inducing kinase (NIK) in cytokine signaling remains controversial. To identify the physiologic functions of NIK, we disrupted the NIK locus by gene targeting. Although NIK–/– mice displayed abnormalities in both lymphoid tissue development and antibody responses, NIK–/– cells manifested normal NF-κB DNA binding activity when treated with a variety of cytokines, including tumor necrosis factor (TNF), interleukin-1 (IL-1), and lymphotoxin-β (LTβ). However, NIK was selectively required for gene transcription induced through ligation of LTβ receptor but not TNF receptors. These results reveal that NIK regulates the transcriptional activity of NF-κB in a receptor-restricted manner.
AAAS