Kinase-inducible domain-like region of HTLV type 1 tax is important for NF-kappa B activation

Partial proteolysis of HTLV-1 Tax protein has revealed the region surroundi ng amino acid residues 88KVL90 to be highly exposed. The protein sequence s urrounding this region ((81)QRTSKTLKVLTPPIT(95)) bears resemblance to the k inase-inducible domain (KID, 129SRRPSYRKILNE140) of CREB and is involved in recruiting transcriptional coactivators, p300 and CBP, for trans-activatin g the viral long terminal repeat (LTR). Data have also revealed the KID-lik e region to be important for Tax binding to DNA, Here we report that single (K88A, V89A, L90A) and double alanine substitutions (V89A-L90A) in the 88K VL90 motif attenuate the ability of Tax to activate NF-kappaB. Deletions ne ar or spanning this motif also had the same effect. The alanine substitutio ns affect HTLV-1 LTR activation and NF-kappaB activation differently, with KSSA and V89A mutants showing much reduced activities for HTLV LTR activati on while retaining attenuated but significant NF-kappaB-activating function . In contrast, although the L90A mutant is similarly attenuated for NF-kapp aB activation, it showed significant activity in LTR trails-activation. Inc orporation of both V89A and L90A substitutions in a V89A-L90A double mutant further reduced NF-kappaB activation and completely abrogated LTR transact ivation. In aggregate, these results demonstrate the importance of the KID- like domain of Tax and implicate its interaction with cellular factors othe r than p300/CBP in NF-kappaB activation.