Cooperativity in Transcription Factor Binding to the Coactivator CREB-binding Protein (CBP). THE MIXED LINEAGE LEUKEMIA PROTEIN (MLL) ACTIVATION DOMAIN BINDS TO AN ALLOSTERIC SITE ON THE KIX DOMAIN Export

@article{citeulike:3024821, abstract = {The interactions between cAMP-response element-binding protein (CREB)-binding protein (CBP) and gene-specific transcription factors play an important role in activation of transcription from numerous genes. Cooperative interactions between CBP and multiple transcriptional activators may provide a mechanism for synergistic increases in transcriptional activation. Here we report the characterization of ternary complexes formed by the KIX domain of CBP and the transactivation domain of the trithorax group protein mixed lineage leukemia protein (MLL), together with either the phosphorylated kinase-inducible domain (pKID) of CREB or the activation domain from c-Myb. Isothermal titration calorimetry experiments show that KIX in complex with the MLL activation domain binds the c-Myb activation domain and pKID domain with 2-fold higher affinity than does the KIX domain alone. Thus, the activation domains of Myb and MLL or of pKID and MLL bind cooperatively to KIX. The thermodynamics of these interactions imply different mechanisms of binding cooperativity for the two ternary complexes; the KIX{middle dot}MLL{middle dot}pKID complex is stabilized by entropy increases, whereas the enhancement of Myb binding in the presence of the MLL activation domain is due to more favorable enthalpy. NMR experiments show that the MLL-binding site on KIX is distinct from the surface that binds the pKID and c-Myb activation domains. Our data indicate that KIX can directly mediate cooperative interactions between pairs of transcriptional regulatory proteins. In the case of MLL and c-Myb, both proteins are involved in proliferation of hematopoietic cells and leukemogenesis, and synergistic interactions mediated by CBP may play a functional role. 10.1074/jbc.M207660200}, author = {Goto, Natalie K. and Zor, Tsaffrir and Martinez-Yamout, Maria and Dyson, Jane H. and Wright, Peter E.}, citeulike-article-id = {3024821}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M207660200}, citeulike-linkout-1 = {http://www.jbc.org/cgi/content/abstract/277/45/43168}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/12205094}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=12205094}, day = {1}, doi = {10.1074/jbc.M207660200}, journal = {J. Biol. Chem.}, keywords = {c-myb, cbp, creb, kid, kix, mll, nmr-structure}, month = {November}, number = {45}, pages = {43168--43174}, posted-at = {2008-07-21 17:05:27}, priority = {2}, title = {Cooperativity in Transcription Factor Binding to the Coactivator CREB-binding Protein (CBP). THE MIXED LINEAGE LEUKEMIA PROTEIN (MLL) ACTIVATION DOMAIN BINDS TO AN ALLOSTERIC SITE ON THE KIX DOMAIN}, url = {http://dx.doi.org/10.1074/jbc.M207660200}, volume = {277}, year = {2002} }

TY - JOUR ID - citeulike:3024821 L3 - citeulike-article-id:3024821 N2 - The interactions between cAMP-response element-binding protein (CREB)-binding protein (CBP) and gene-specific transcription factors play an important role in activation of transcription from numerous genes. Cooperative interactions between CBP and multiple transcriptional activators may provide a mechanism for synergistic increases in transcriptional activation. Here we report the characterization of ternary complexes formed by the KIX domain of CBP and the transactivation domain of the trithorax group protein mixed lineage leukemia protein (MLL), together with either the phosphorylated kinase-inducible domain (pKID) of CREB or the activation domain from c-Myb. Isothermal titration calorimetry experiments show that KIX in complex with the MLL activation domain binds the c-Myb activation domain and pKID domain with 2-fold higher affinity than does the KIX domain alone. Thus, the activation domains of Myb and MLL or of pKID and MLL bind cooperatively to KIX. The thermodynamics of these interactions imply different mechanisms of binding cooperativity for the two ternary complexes; the KIX{middle dot}MLL{middle dot}pKID complex is stabilized by entropy increases, whereas the enhancement of Myb binding in the presence of the MLL activation domain is due to more favorable enthalpy. NMR experiments show that the MLL-binding site on KIX is distinct from the surface that binds the pKID and c-Myb activation domains. Our data indicate that KIX can directly mediate cooperative interactions between pairs of transcriptional regulatory proteins. In the case of MLL and c-Myb, both proteins are involved in proliferation of hematopoietic cells and leukemogenesis, and synergistic interactions mediated by CBP may play a functional role. 10.1074/jbc.M207660200 IS - 45 JF - J. Biol. Chem. EP - 43174 TI - Cooperativity in Transcription Factor Binding to the Coactivator CREB-binding Protein (CBP). THE MIXED LINEAGE LEUKEMIA PROTEIN (MLL) ACTIVATION DOMAIN BINDS TO AN ALLOSTERIC SITE ON THE KIX DOMAIN VL - 277 SP - 43168 KW - c-myb KW - cbp KW - creb KW - kid KW - kix KW - mll KW - nmr-structure AU - Goto, Natalie AU - Zor, Tsaffrir AU - Martinez-Yamout, Maria AU - Dyson, Jane AU - Wright, Peter PY - 2002/11/01/ UR - http://dx.doi.org/10.1074/jbc.M207660200 ER -