Tumor necrosis factor receptor-associated factor (TRAF)2 represses the T helper cell type 2 response through interaction with NFAT-interacting protein (NIP45).
Recently we have identified a novel protein NIP45 (nuclear factor of activated T cells [NFAT]-interacting protein) which substantially augments interleukin (IL)-4 gene transcription. The provision of NIP45 together with NFAT and the T helper cell type 2 (Th2)-specific transcription factor c-Maf to cells normally refractory to IL-4 production, such as B cells or Th1 clones, results in substantial IL-4 secretion to levels that approximate those produced by primary Th2 cells. In studies designed to further our understanding of NIP45 activity, we have uncovered a novel facet of IL-4 gene regulation. We present evidence that members of the tumor necrosis factor receptor-associated factor (TRAF) family of proteins, generally known to function as adapter proteins that transduce signals from the tumor necrosis factor receptor superfamily, contribute to the repression of IL-4 gene transcription and that this effect is mediated through their interaction with NIP45.
Lieberson
R
R
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Mowen
K A
KA
McBride
K D
KD
Leautaud
V
V
Zhang
X
X
Suh
W K
WK
Wu
L
L
Glimcher
L H
LH
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D015847:Interleukin-4 / Q000235:genetics* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*; D047992:TNF Receptor-Associated Factor 2; D018418:Th2 Cells / Q000502:physiology; D014158:Transcription, Genetic
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C102566:Nfatc2ip protein, mouse; D009687:Nuclear Proteins; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D047992:TNF Receptor-Associated Factor 2; D015847:Interleukin-4