Inhibition of JNK activation through NFkB target genes

1
Inhibition of JNK activation through NF-kB target
genes GUILIN TANG, YUZURU MINEMOTO,
BENJAMIN DIBLING, NICOLE H. PURCELL,
ZHIWEI LI, MICHAEL KARIN ANNING LIN  Ben
May Institute for Cancer Research, Committee on
Cancer Biology, University of Chicago, 5841 S.
Maryland Avenue, MC 6027, Chicago, Illinois
60637,  Laboratory of Gene Regulation and
Signal Transduction, Department of Pharmacology,
University of California, San Diego, 9500
Gilman Drive, La Jolla, California 92093-0636,
 These authors contributed equally to the
work Correspondence and requests for materials
should be addressed to A.L. (email
alin_at_huggins.bsd.uchicago.edu).
2
(No Transcript)
3
Effect of IKK/NF-kB signaling pathway on the
activation of JNK by TNF-a
4
NF-kB mediates the inhibitory effect of IKK on JNK
5

• Possibile mechanism for the inactivation
  of JNK
• Dephosphorylation of JNK by phosphatase induced
  by IKK/NF-kB signaling pathway
• Other NF-kB-induced inhibitors of JNK
  activationNF-kB-terget gene XIAP, c-IAP1,
  BCl-XL, Bcl-2 etc.XIAP X-chromosome-linked
  inhibitor of apoptosis protein- direct binding
  and inhibition of caspases (3, 7, 9)

6
Inhibition of JNK activation by NF-kB is specific
to TNF-a signaling and involves XIAP, but not
phosphatases.
UV-HeLa
Microcystin S/T phosphatase Vanadate Y
phoaphatase
7
(No Transcript)
8
(No Transcript)
9
TNF-a killing of RelA-/- fibroblast is inhibited
by a DN JNKK2 mutant but enhanced by a
constitutively active JNKK2-JNK1 fusion protein
Constitutively Active


JNKK2(K149M)-JNK1