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Basic Characteristics of Mutations
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Mutation Site
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K88A |
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Mutation Site Sentence
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Here we report that single (K88A, V89A, L90A) and double alanine substitutions (V89A-L90A) in the (88)KVL(90) motif attenuate the ability of Tax to activate NF-kappaB. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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tax |
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Standardized Encoding Gene
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tax
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Genotype/Subtype
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- |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Cell line
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Immune
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- |
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Target Gene
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CREB1
EP300
CREBBP
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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11080799
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Title
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Kinase-inducible domain-like region of HTLV type 1 tax is important for NF-kappaB activation
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Author
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Kuo YL,Tang Y,Harrod R,Cai P,Giam CZ
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Journal
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AIDS research and human retroviruses
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Journal Info
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2000 Nov 1;16(16):1607-12
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Abstract
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Partial proteolysis of HTLV-1 Tax protein has revealed the region surrounding amino acid residues (88)KVL(90) to be highly exposed. The protein sequence surrounding this region ((81)QRTSKTLKVLTPPIT(95)) bears resemblance to the kinase-inducible domain (KID, (129)SRRPSYRKILNE(140)) of CREB and is involved in recruiting transcriptional coactivators, p300 and CBP, for trans-activating the viral long terminal repeat (LTR). Data have also revealed the KID-like 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 (88)KVL(90) motif attenuate the ability of Tax to activate NF-kappaB. Deletions near or spanning this motif also had the same effect. The alanine substitutions affect HTLV-1 LTR activation and NF-kappaB activation differently, with K88A and V89A mutants showing much reduced activities for HTLV LTR activation while retaining attenuated but significant NF-kappaB-activating function. In contrast, although the L90A mutant is similarly attenuated for NF-kappaB activation, it showed significant activity in LTR trans-activation. Incorporation of both V89A and L90A substitutions in a V89A-L90A double mutant further reduced NF-kappaB activation and completely abrogated LTR trans-activation. In aggregate, these results demonstrate the importance of the KID-like domain of Tax and implicate its interaction with cellular factors other than p300/CBP in NF-kappaB activation.
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Sequence Data
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-
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