生物谷報(bào)道：c-Myc最初是作為一個(gè)原致癌基因發(fā)現(xiàn)的,，活躍于很多人類腫瘤中,，但它也是一種轉(zhuǎn)錄因子,，是正常細(xì)胞生長和增殖所必需的。因此,，它影響基因表達(dá)的能力過去曾被認(rèn)為是其促進(jìn)腫瘤發(fā)育的手段,。但最近關(guān)于c-Myc也影響DNA復(fù)制的發(fā)現(xiàn)直接表明，對于它的某些作用應(yīng)有另一種解釋,。發(fā)表在最新一期《自然》雜志上的一篇報(bào)道對此進(jìn)行了闡述,。
研究人員發(fā)現(xiàn)，通過定位DNA合成點(diǎn)及與復(fù)制前復(fù)合體相結(jié)合,，c-Myc能夠控制DNA復(fù)制,；當(dāng)失控時(shí)，同一機(jī)制也許還能引起DNA損傷和不正確的細(xì)胞增殖,，從而引起癌癥的發(fā)生,。
原文出處：
Non-transcriptional control of DNA replication by c-Myc p445
David Dominguez-Sola, Carol Y. Ying, Carla Grandori, Luca Ruggiero, Brenden Chen, Muyang Li, Denise A. Galloway, Wei Gu, Jean Gautier & Riccardo Dalla-Favera
doi:10.1038/nature05953
Abstract | Full Text | PDF (991K) | Supplementary information
See also: Editor's summary
相關(guān)基因：
MYC
Official Symbol MYC and Name: v-myc myelocytomatosis viral oncogene homolog (avian) [Homo sapiens]
Other Aliases: c-Myc
Other Designations: avian myelocytomatosis viral oncogene homolog; myc proto-oncogene protein; v-myc avian myelocytomatosis viral oncogene homolog
Chromosome: 8; Location: 8q24.21
Annotation: Chromosome 8, NC_000008.9 (128817498..128822856)
MIM: 190080
GeneID: 4609
作者簡介：
Riccardo Dalla-Favera, M.D.
Director, Institute for Cancer Genetics
Professor
Identification of the Genetic Lesions Involved in the Pathogenesis of Human B Cell Tumors
The development of many types of cancer is due to genetic lesions involving proto-oncogenes and tumor suppressor genes. It is well established that multiple lesions must occur in a cell before cancer can develop. The general goal of this laboratory is to identify the lesions and the genes involved in the development of human B cell lymphoma, to determine the mechanism by which these lesions occur and to elucidate the contribution of each lesion to tumor development.
Specific lines of investigation include:
(1) Elucidating the role of chromosomal translocations involving the c-myc proto oncogene locus and immuno-globulin loci in the development of Burkitt's lymphoma. These studies include the analysis of the mechanisms regulating the expression of the normal c-myc gene as well as of c-myc alleles structurally altered by chromosomal translocation in lymphoma cells.
(2) Studying the normal and pathologic function of the BCL-6 gene, a recently identified proto-oncogene which codes for a transcription factor expressed in B cells and is altered in its regulatory region in a significant fraction of human lymphoma.
(3) Identifying novel oncogenes and tumor suppressors involved in the pathogenesis of lymphoma by virtue of their involvement in tumor-associated chromosomal translocations or by "positional cloning" from chromosomal regions involved in tumor-associated deletions.
Selected Publications
Niu, H., Ye, B-H., and Dalla-Favera, R. Antigen-Receptor Signaling Induces MAP Kinase-Mediated Phosphorylation and Degradation of the BCL-6 Transcription Factor. Genes & Dev., 12(13): 1953-1961 (1998).
Pasqualucci, L., Migliazza, A., Fracchiolla N., William C., Neri, A., Baldini, L., Chaganti, R.S.K., Klein, U., Kueppers, R., Rajewsky, K., Dalla-Favera, R. BCL-6 mutations in normal germinal center B cells: Evidence of somatic hypermutation acting outside Ig loci. Proc Natl Acad Sci (USA), 95: 11816-11821, (1998).
Wu, K.-J., Dalla-Favera, R. Direct activation of telomerase reverse transcriptase (hTERT) gene transcription by c-MYC. Nature Genetics, 21: 220-224 (1999). Wu, K-J., Polack, A., Dalla-Favera, R. (1999).
Wu, K.-J., Polack, A., Dalla-Favera, R. Coordinated regulation of iron-controlling genes, H-Ferritin and IRP2, by c-Myc. Science, 283: 676-679 (1999).
Pasqualucci L, Neumeister P, Goossens T, Nanjangud G, Chaganti RS, Kuppers R, Dalla-Favera R. Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas. Nature, 19:341-346 (2001).
Klein, U., Tu, Y., Stolovitzky, G.A., Mattioli, M., Cattoretti, G., Husson, H., Freedman, A., Inghirami, G., Cro, L., Baldini, L., Neri, A., Califano, A., Dalla-Favera, R. Gene expression profiling of B cell chronic lymphocytic leukemia reveals a homogenous phenotype related to memory B cells. J. Exp Med, 97: 2098-2104 (2001) (Supplementary Data)
Klein, U., Gloghini, A., Gaidano, G., Chadburn, A., Cesarman, E., Dalla-Favera, R., Carbone, A. Gene expression profile analysis of AIDS-related primary effusion lymphoma (PEL) suggests a plasmablastic derivation and identifies PEL-specific transcripts. Blood First Edition Paper, prepublished online January 16, 2003 (Supplementary Data)
Klein, U., Tu, Y., Stolovitzky, G.A., Keller, J.L., Haddad Jr., J., Miljkovic, V., Cattoretti, G., Califano, A., Dalla-Favera, R. Transcriptional Analysis of the B-Cell Germinal Center Reaction. Proc. Acad. Natl. Sci. U. S. A. 100:2639-2644, 2003 (Supplementary Data)
Küppers, R., U. Klein, I. Schwering, V. Distler, A. Bräuninger, G. Cattoretti, Y. Tu, G.A. Stolovitzky, A. Califano, M.-L. Hansmann, and R. Dalla-Favera. Identification of Hodgkin and Reed-Sternberg Cell-Specific Genes by Gene Expression Profiling. J. Clin. Invest. 111:529-537, 2003 (Supplementary Data)
Basso, K., Liso, A., Tiacci, E., Benedetti, R., Pulsoni, A., Foa, R., Di Raimondo, F., Ambrosetti, A., Califano, A., Klein, U., Dalla-Favera, R., Falini, B. Gene expression profiling of hairy cell leukemia reveals a phenotype related to memory B cells with altered expression of chemokine and adhesion receptors. J. Exp. Med. 199 (1): 59-68. (Supplementary Data)
Basso, K., Klein, U., Niu, H., Stolovitzky G.A., Tu, Y., Califano, A., Cattoretti, G., and Dalla-Favera, R. Tracking CD40 signaling during germinal center development Blood 104 (13): 4088-4096 2004. (Supplementary Data)
