@article {934,
	title = {Diversity in structure and function of the Ets family PNT domains},
	journal = {Journal of Molecular Biology},
	volume = {342},
	number = {4},
	year = {2004},
	note = {ISI Document Delivery No.: 855WLTimes Cited: 17Cited Reference Count: 86},
	month = {Sep},
	pages = {1249-1264},
	type = {Article},
	abstract = {The PNT (or Pointed) domain, present within a subset of the Ets family of transcription factors, is structurally related to the larger group of SAM domains through a common tertiary arrangement of four alpha-helices. Previous studies have shown that, in contrast to the PNT. domain from Tel, this domain from Ets-1 contains an additional N-terminal helix integral to its folded structure. To further investigate the structural plasticity of the PNT domain, we have used NMR spectroscopy to characterize this domain from two additional Ets proteins, Erg and GABPalpha. These studies both define the conserved and variable features of the PNT domain, and demonstrate that the additional N-terminal helix is also present in GABPa, but not Erg. In contrast to Tel and Yan, which self-associate to form insoluble polymers, we also show that the isolated PNT domains from Ets-1, Ets-2, Erg, Fli-1, GABPalpha, and Pnt-P2 are monomeric in solution. Furthermore, these soluble PNT domains do not associate in any pair-wise combination. Thus these latter Ets family PNT domains likely mediate interactions with additional components of the cellular signaling or transcriptional machinery. (C) 2004 Elsevier Ltd. All rights reserved.},
	keywords = {ALPHA-MOTIF SAM, ASSIGNMENT, AUTOMATED, CHEMICAL-SHIFT, DIPOLAR COUPLINGS, ENDOTHELIAL-CELL DIFFERENTIATION, Erg, GABP, GENE, NMR-SPECTRA, POINTED DOMAIN, protein interactions, PROTEIN-KINASE, SAM domain, TRANSCRIPTION FACTOR},
	isbn = {0022-2836},
	url = {<Go to ISI>://000224005500015},
	author = {Mackereth, C. D. and Scharpf, M. and Gentile, L. N. and Macintosh, S. E. and Slupsky, C. M. and McIntosh, L. P.}
}
@article {1019,
	title = {Mutations in the SAM domain of the ETV6-NTRK3 chimeric tyrosine kinase block polymerization and transformation activity},
	journal = {Molecular and Cellular Biology},
	volume = {24},
	number = {11},
	year = {2004},
	note = {ISI Document Delivery No.: 822JXTimes Cited: 12Cited Reference Count: 53},
	month = {Jun},
	pages = {4636-4650},
	type = {Article},
	abstract = {The 12p13 ETV6 (TEL) gene is frequently targeted by chromosomal translocations in human malignancies, resulting in the formation of oncogenic ETV6 gene fusions. Many of the known partner genes encode protein tyrosine kinases (PTKs), generating fusion proteins that function as chimeric PTKs. ETV6-NTRK3 (EN), comprised of the ETV6 SAM domain fused to the NTRK3 PTK, is unique among ETV6 chimeric oncoproteins, as it is expressed in cancers of multiple lineages. We initially hypothesized that, similar to other ETV6-PTK chimeras, SAM-mediated dimerization of EN leads to constitutive activation of the PTK and downstream signaling cascades. However, when the EN SAM domain was replaced with an inducible FK506 binding protein (FKBP) dimerization system, resulting FKBP-NTRK3 chimeras failed to transform NIH 3T3 cells even though PTK activation was preserved. It was recently shown that the ETV6 SAM domain has two potential interacting surfaces, raising the possibility that this domain can mediate protein polymerization. We therefore mutated each EN SAM binding interface in a manner shown previously to abolish self-association of wild-type ETV6. Each mutation completely blocked the ability of EN to polymerize, to activate its PTK, and to transform NIH 3T3 cells. Furthermore, EN itself formed large polymeric structures within cells while mutant EN proteins were present only as monomers. Finally, we observed a dominant negative effect on the transformation of isolated SAM domains coexpressed in EN-transformed cells. Taken together, our results suggest that higher-order polymerization may be a critical requirement for the transformation activity of EN and possibly other ETV6-PTK fusion proteins.},
	keywords = {ABL-RELATED GENE, ACUTE LYMPHOBLASTIC-LEUKEMIA, BCR-ABL, CHROMOSOMAL TRANSLOCATION, CHRONIC MYELOMONOCYTIC LEUKEMIA, CONGENITAL FIBROSARCOMA, FUSION PROTEIN, INTERFACE, MYELOID-LEUKEMIA, OLIGOMERIZATION, PROTEIN-KINASE},
	isbn = {0270-7306},
	url = {<Go to ISI>://000221536600004},
	author = {Tognon, C. E. and Mackereth, C. D. and Somasiri, A. M. and McIntosh, L. P. and Sorensen, P. H. B.}
}
@article {480,
	title = {Oligomerization-dependent association of the SAM domains from Schizosaccharomyces pombe Byr2 and Ste4},
	journal = {Journal of Biological Chemistry},
	volume = {277},
	number = {42},
	year = {2002},
	note = {ISI Document Delivery No.: 605EATimes Cited: 21Cited Reference Count: 46},
	month = {Oct},
	pages = {39585-39593},
	type = {Article},
	abstract = {SAM (sterile alpha motif) domains are protein-protein interaction modules found in a large number of regulatory proteins. Byr2 and Ste4 are two SAM domain-containing proteins in the mating pheromone response pathway of the fission yeast, Schizosaccharomyces pombe. Byr2 is a mitogen-activated protein kinase kinase kinase that is regulated by Ste4. Tu et al (Tu, H., Barr, M., Dong, D. L., and Wigler, M. (1997) Mol. Cell. Biol. 17, 5876-5887) showed that the isolated SAM domain of Byr2 binds a fragment of Ste4 that contains both a leucine zipper (Ste4-LZ) domain as well as a SAM domain, suggesting that Byr2-SAM and Ste4-SAM may form a hetero-oligomer. Here, we show that the individual SAM domains of Ste4 and Byr2 are monomeric at low concentrations and bind to each other in a 1:1 stoichiometry with a relatively weak dissociation constant of 56 +/- 3 mum. Inclusion of the Ste4-LZ domain, which determines the oligomeric state of Ste4, has a dramatic effect on binding affinity, however. We find that the Ste4-LZ domain is trimeric and, when included with the Ste4-SAM domain, yields a 3:1 Ste4-LZ-SAM:Byr2-SAM complex with a tight dissociation constant of 19 +/- 4 nm. These results suggest that the Ste4-LZ-SAM protein may recognize multiple binding sites on Byr2-SAM, indicating a new mode of oligomeric organization for SAM domains. The fact that high affinity binding occurs only with the addition of an oligomerization domain suggests that it may be necessary to include ancillary oligomerization modules when searching for binding partners of SAM domains.},
	keywords = {CRYSTAL-STRUCTURE, HUMAN LEUKEMIA, IDENTIFICATION, KINASE, LAC REPRESSOR, PROTEIN-KINASE, RECEPTOR, TEL, TRANSCRIPTION FACTOR, TYROSINE, YEAST},
	isbn = {0021-9258},
	url = {<Go to ISI>://000178662500069},
	author = {Ramachander, R. and Kim, C. A. and Phillips, M. L. and Mackereth, C. D. and Thanos, C. D. and McIntosh, L. P. and Bowie, J. U.}
}
@article {5181,
	title = {G(2) DNA damage checkpoint inhibition and antimitotic activity of 13-hydroxy-15-oxozoapatlin},
	journal = {Journal of Biological Chemistry},
	volume = {276},
	number = {51},
	year = {2001},
	note = {ISI Document Delivery No.: 505QLTimes Cited: 24Cited Reference Count: 51},
	month = {Dec},
	pages = {48231-48236},
	type = {Article},
	abstract = {Checkpoints activated in response to DNA damage cause arrest in the G(1) and G(2) phases of the cell cycle. Inhibitors of the G(2) checkpoint may be used as tools to study this response and also to increase the effectiveness of DNA-damaging therapies against cancers lacking p53 function. Using a cell-based assay for G(2) check. point inhibitors, we have screened extracts from the NCI National Institutes of Health Natural Products Repository and have identified 13-hydroxy-15-oxozoapatlin (OZ) from the African tree Parinari curatellifolia. Flow cytometry with a mitosis-specific antibody showed that checkpoint inhibition by OZ was maximal at 10 muM, which released 20\% of irradiated MCF-7 cells expressing defective p53 and 30\% of irradiated HCT116p53(-/-) cells from G(2) arrest. OZ additively increased the response to the checkpoint inhibitors isogranulatimide and debromohymenialdisine, but it did not augment the effects of UCN-01 or caffeine. Unlike other checkpoint inhibitors, OZ did not inhibit ataxia-telangiectasia mutated (ATM), ATM and Rad3-related (ATR), Chk1, Chk2, Plk1, or Ser/Thr protein phosphatases in vitro. Treatment with OZ also caused G(2)-arrested and cycling cells to arrest in mitosis in a state resembling prometaphase. In these cells, the chromosomes were condensed and scattered over disordered mitotic spindles. The results demonstrate that OZ is both a G(2) checkpoint inhibitor and an antimitotic agent.},
	keywords = {ARREST, BHK CELLS, CAFFEINE, CELL-CYCLE CHECKPOINTS, CHROMOSOME ALIGNMENT, G2, P34(CDC2) KINASE, PROTEIN-KINASE, RADIOSENSITIZING AGENT, TYROSINE KINASE, UCN-01},
	isbn = {0021-9258},
	url = {<Go to ISI>://000172927000066},
	author = {Rundle, N. T. and Xu, L. and Andersen, R. J. and Roberge, M.}
}
@article {4194,
	title = {Granulatimide and isogranulatimide, aromatic alkaloids with G2 checkpoint inhibition activity isolated from the Brazilian ascidian Didemnum granulatum: Structure elucidation and synthesis},
	journal = {Journal of Organic Chemistry},
	volume = {63},
	number = {26},
	year = {1998},
	note = {ISI Document Delivery No.: 153LPTimes Cited: 72Cited Reference Count: 34},
	month = {Dec},
	pages = {9850-9856},
	type = {Article},
	abstract = {Crude methanol ex-tracts of the ascidian Didemum granulatum collected in Brazil showed activity in a new screen for G2 cell cycle checkpoint inhibitors. Bioassay-guided fractionation of the extract yielded the known alkaloids didemnimides A (1) and D (2), the new alkaloid didemnimide E (3), and a new G2 checkpoint inhibitor. Two candidate structures for the inhibitor, named granulatimide (4) and isogranulatimide (5), have been prepared via a short and efficient biomimetic synthesis involving the photolysis of didemnimide A (1). The synthesis revealed that the correct structure for the naturally occurring G2 checkpoint inhibitor is isogranulatimide (5). Granulatimide (4), the other candidate structure, was also found to be a G2 checkpoint inhibitor, and it was subsequently detected in chromatographic fractions associated with purification of D. granulatum alkaloids. Granulatimide (4) and isogranulatimide (5) represent the first examples of a new class of G2 specific cell cycle checkpoint inhibitors and the first ones identified through a rational screening program.},
	keywords = {BHK CELLS, CAFFEINE, CELL-CYCLE CHECKPOINTS, DNA-REPLICATION, HELA-CELLS, INDUCED G(2) DELAY, mitosis, PROTEIN-KINASE, RADIOSENSITIZATION, STAUROSPORINE},
	isbn = {0022-3263},
	url = {<Go to ISI>://000077834800044},
	author = {Berlinck, R. G. S. and Britton, R. and Piers, E. and Lim, L. and Roberge, M. and da Rocha, R. M. and Andersen, R. J.}
}
