生物谷报道：c-Myc最初是作为一个原致癌基因发现的，活跃于很多人类肿瘤中，但它也是一种转录因子，是正常细胞生长和增殖所必需的。因此，它影响基因表达的能力过去曾被认为是其促进肿瘤发育的手段。但最近关于c-Myc也影响DNA复制的发现直接表明，对于它的某些作用应有另一种解释。发表在最新一期《自然》杂志上的一篇报道对此进行了阐述。
研究人员发现，通过定位DNA合成点及与复制前复合体相结合，c-Myc能够控制DNA复制；当失控时，同一机制也许还能引起DNA损伤和不正确的细胞增殖，从而引起癌症的发生。
原文出处：
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
相关基因：
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
作者简介：
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)
