TRAF6-regulated IKK activators (TRIKA1 and TRIKA2) and their use as anti-inflammatory targets

A method of screening for modulators of IKK and JNK activation comprising:

• (a) providing a TRAF2 or a TRAF6;
• (b) contacting TRAF2 or TRAF6 with a candidate modulator substance in the presence of E1, Ubc13/Uev1A, a plurality of ubiquitin molecules and ATP;
• (c) determining the ubiquitin ligase activity of TRAF2 or TRAF6,
• wherein a change in the enzyme activity of TRAF2 or TRAF6 in the presence of said candidate modulator, as compared with the activity of TRAF2 or TRAF6 in the absence of said candidate modulator, indicates that said candidate modulator is an modulator of IKK and JNK activation.

A method of screening for modulators of IKK and JNK activation comprising:

• (a) providing TAK1, TAB 1, TRAF6 and TAB2;
• (b) contacting TAK1, TAB 1, TRAF6 and TAB2 with a candidate modulator substance in the presence of E1, Ubc13/Uev1A, a plurality of ubiquitin molecules and ATP;
• (c) determining the kinase activity of TAK 1,
• wherein a change in the kinase activity of TAK1 in the presence of said candidate modulator, as compared with the kinase activity of TAK1 in the absence of said candidate modulator, indicates that said candidate modulator is an modulator of IKK and JNK activation.

A method of screening for modulators of IKK and JNK activation comprising:

• (a) providing TAK1, TAB 1, TAB2, TRAF6 and IKK complex;
• (b) contacting TAK1, TAB1, TAB2, TRAF6 and IKK complex with a candidate modulator substance in the presence of E1, Ubc13/Uev1A, a plurality of ubiquitin molecules and ATP;
• (c) determining the phosphorylation state of IκB and MKK,
• wherein a change in the phosphorylation state of IκB and MKK in the presence of said candidate modulator, as compared with the phosphorylation state of IκB and MKK in the absence of said candidate modulator, indicates that said candidate modulator is an modulator of IKK and JNK activation.