Open AccessStructural basis for cooperative regulation of KIX-mediated transcription pathways by the HTLV-1 HBZ activation domain
Author(s) -
Ke Yang,
Robyn L. Stanfield,
Maria A. MartinezYamout,
H. Jane Dyson,
Ian A. Wilson,
Peter E. Wright
Publication year - 2018
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1810397115
Subject(s) - cooperativity , transcription factor , coactivator , creb binding protein , ternary complex , transcription (linguistics) , plasma protein binding , leucine zipper , biology , transactivation , creb , binding site , myb , isothermal titration calorimetry , dna binding protein , microbiology and biotechnology , biophysics , genetics , biochemistry , linguistics , philosophy , gene , enzyme
Significance The human T cell leukemia virus I basic leucine zipper protein (HBZ) plays a central role in leukemogenesis and proliferation of transformed adult T cell leukemia cells. Through its interactions with the KIX domain of the transcriptional coactivators CBP and p300, HBZ deregulates transcriptional programs involved in hematopoietic differentiation. Here, we describe the crystal structure of the ternary complex formed between KIX and the activation domains of HBZ and the cellular transcription factor c-Myb. By binding to KIX to form the ternary complex, HBZ allosterically stabilizes the interaction between KIX and c-Myb. These studies provide molecular insights into the mechanism by which HBZ interferes with hematopoietic signaling pathways and promotes T cell proliferation.
Accelerating Research
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom
Address
John Eccles HouseRobert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom