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S.R. Jordan, C.O. Pabo, "Structure of the lambda-complex at 2.5 Å resolution: Details of the repressor-operator interactions," Science, 242, 893-9, 11 November 1988. Steve Jordan (Agouron Pharmaceuticals Inc., La Jolla, Calif.): "The structure of the lambda repressor-operator complex was of great interest not only because it tied together a wealth of experimental data concerning the specific question of how lambda repressor binds to its operator, DNA, but also because the structure gave new insights into the general question of how proteins recognize a specific sequence of B-form DNA. "The cocrystal structure confirmed the general features of a previous model, which was based upon the structure of the protein alone. But certain details of that model were shown to be incorrect. The cocrystal structure also explained some experimental data that could not be explained by the earlier model, such as how the N-terminal arm of repressor is used in recognition. "Another exciting aspect of the cocrystal structure was that the structures of two other repressor-operator complexes were solved at approximately the same time. Both the repressor from the phage 434 and the E. coli trp repressor, like the lambda repressor, use a helix-turn-helix motif to bind in the major groove of their respective operator sites. Analysis of this trio of cocrystal structures shows that there is not a simple `recognition code.' Instead, proteins recognize their target DNA sequence by an intricate and detailed set of interactions with the DNA bases and the phosphate backbone." R.G. Clerc, L.M. Corcoran, J.H. LeBowitz, D. Baltimore, P.A. Sharp, "The B-cell-specific Oct-2 protein contains POU box- and homeo box-type domains," Genes and Development, 2, 1570-81, December 1988. Phillip A. Sharp (Center for Cancer Research, Massachusetts Institute of Technology, Cambridge): "The cell-type-specific synthesis of proteins has long fascinated molecular and developmental biologists; B-lymphocyte-specific transcription of immunoglobulin genes has been a primary model of this phenomenon. The major promoter/enhancer sequence element responsible for this B-cell-specific transcription is an octamer sequence (ATGCAAAT). Paradoxically, the same sequence element is also active in the transcription of many genes expressed in diverse cell types. B-cells synthesize two proteins that recognize the octamer sequence, and one of these proteins is ubiquitously expressed. The cloning of a cDNA for the B-cell-specific protein Oct-2 and comparison of its sequence with the cDNA encoding the ubiquitous factor Oct-1 extended the apparent paradox of the specific functions of these two proteins. Both proteins contained a highly homologous homeobox domain explaining their similar DNA binding specificities. Both proteins also contained an even more highly conserved 75 amino acid domain called the Pou-specific box. These two domains are collectively referred to as the Pou domain. "A related set of domains was found in a factor expressed in pituitary cells that controls growth hormone and prolactin synthesis (Pit-1) and in the protein encoded by the unc-86 gene of the nematode C. elegans. Thus, Pou was coined from Pit-1, Octa, and Unc-86. The highly conserved Pou-specific box must have an important role in the activities of these regulatory proteins. (Note: The common structure among these proteins is pronounced pow, and not poo, as we would not want the model of their common activity poo-pooed.)" M.J. van de Vijver, J.L. Peterse, W.J. Mooi, P. Wisman, et al., "Neu-protein overexpression in breast cancer: Association with comedo-type ductal carcinoma in situ and limited prognostic value in Stage II breast cancer," New England Journal of Medicine, 319, 1239-45, 10 November 1988. Marc J. van de Vijver (Division of Molecular Biology, Netherlands Cancer Institute, Amsterdam): "We think our paper has attracted attention for three reasons. First, we described the first monoclonal antibodies against neu protein that detect neu protein in immunohistochemistry on routine paraffin sections of breast tumors where the neu gene is amplified. Secondly, initial reports suggested that neu gene amplification in breast cancer was very strongly correlated to poor prognosis. This suggested that this parameter could have important consequences for patients with this disease. Our findings indicated, however, that neu protein overexpression had only a weak correlation with poor prognosis. Therefore, neu gene amplification and overexpression should be viewed as a very interesting research area, but without dramatic impact on clinical medicine. "And lastly, we found neu protein overexpression to be specifically associated with ductal carcinoma in situ with a comedo growth pattern. This identifies neu overexpression as an early event in a specific subgroup of breast carcinomas. We think this identifies neu gene amplification as a pathogenetic factor in this group of breast carcinomas.

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