TY - JOUR
T1 - X-ray structures of Myc-Max and Mad-Max recognizing DNA
T2 - Molecular bases of regulation by proto-oncogenic transcription factors
AU - Nair, Satish K.
AU - Burley, Stephen K.
N1 - Funding Information:
At the National Synchrotron Light Source, we thank Drs. K.R. Rajashankar and Z.B. Dauter for support at Beamline X9B, and Dr. H. Lewis for support at Beamline X25; and at Argonne National Laboratories, we thank Drs. A. Joachimiak, S.L. Ginell, and F.J. Rotella for support at Beamline ID19. We thank Dr. J.B. Bonanno for assistance with data collection and Carme Edo and Hua Chen for technical help. We are grateful to Drs. R.N. Eisenman, D. Ayer, E. Ziff, T. Halazonetis, A. Ferre-D'Amare, A. Parraga, and C. Dang for providing cDNA clones and for insightful comments on Myc biology and bHLHZ structures. We also thank Drs. E.A. Campbell, S.A. Darst, R.C. Deo, K.S. Gajiwala, M. Huse, J. Kuriyan, T. Muir, and M. Young for many useful discussions. S.K.B. is an Investigator in the Howard Hughes Medical Institute. This work was supported by a grant from the N.I.H. S.K.N. was supported by a Leukemia Society of America postdoctoral fellowship and the Howard Hughes Medical Institute.
PY - 2003/1/24
Y1 - 2003/1/24
N2 - X-ray structures of the basic/helix-loop-helix/leucine zipper (bHLHZ) domains of Myc-Max and Mad-Max heterodimers bound to their common DNA target (Enhancer or E box hexanucleotide, 5′-CACGTG-3′) have been determined at 1.9 Å and 2.0 Å resolution, respectively. E box recognition by these two structurally similar transcription factor pairs determines whether a cell will divide and proliferate (Myc-Max) or differentiate and become quiescent (Mad-Max). Deregulation of Myc has been implicated in the development of many human cancers, including Burkitt's lymphoma, neuroblastomas, and small cell lung cancers. Both quasisymmetric heterodimers resemble the symmetric Max homodimer, albeit with marked structural differences in the coiled-coil leucine zipper regions that explain preferential homo- and heteromeric dimerization of these three evolutionarily related DNA-binding proteins. The Myc-Max heterodimer, but not its Mad-Max counterpart, dimerizes to form a bivalent heterotetramer, which explains how Myc can upregulate expression of genes with promoters bearing widely separated E boxes.
AB - X-ray structures of the basic/helix-loop-helix/leucine zipper (bHLHZ) domains of Myc-Max and Mad-Max heterodimers bound to their common DNA target (Enhancer or E box hexanucleotide, 5′-CACGTG-3′) have been determined at 1.9 Å and 2.0 Å resolution, respectively. E box recognition by these two structurally similar transcription factor pairs determines whether a cell will divide and proliferate (Myc-Max) or differentiate and become quiescent (Mad-Max). Deregulation of Myc has been implicated in the development of many human cancers, including Burkitt's lymphoma, neuroblastomas, and small cell lung cancers. Both quasisymmetric heterodimers resemble the symmetric Max homodimer, albeit with marked structural differences in the coiled-coil leucine zipper regions that explain preferential homo- and heteromeric dimerization of these three evolutionarily related DNA-binding proteins. The Myc-Max heterodimer, but not its Mad-Max counterpart, dimerizes to form a bivalent heterotetramer, which explains how Myc can upregulate expression of genes with promoters bearing widely separated E boxes.
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U2 - 10.1016/S0092-8674(02)01284-9
DO - 10.1016/S0092-8674(02)01284-9
M3 - Article
C2 - 12553908
AN - SCOPUS:0037462459
SN - 0092-8674
VL - 112
SP - 193
EP - 205
JO - Cell
JF - Cell
IS - 2
ER -