Molecular cloning, chromosomal mapping, and expression of the mouse p107 gene
Tóm tắt
Progression through the G1 phase of the cell cycle is regulated, in part, by the pRB-family proteins, pRB and p107. The basis for this regulation is due to a network of interactions between the pRB-family proteins, pRB, pl07, and pl30; the E2F-family of transcription factors; and cyclins D, E, and A. One of the pRB-family proteins, p107, has also been found to bind to the transactivation domain of the c-Myc proto-oncogene. This region in c-Myc is frequently mutated in tumors such as Burkitt’s lymphoma, HIV-associated lymphoma, and multiple myeloma. The binding of p107 and regulation of c-Myc may conceivably be disrupted not only by mutations in c-Myc, but possibly by mutations in p107. In order to determine if mutations in p107 are indeed present in mouse B-cell tumors which exhibit a lower frequency of c-Myc mutation, we have cloned the mouse p107 cDNA and compared this sequence with its human counterpart. We find that the extreme N-terminal and C-terminal regions are the most conserved between human and mouse p107 sequences. Chromosomal positioning of the locus for p107 (designated Rbl1) as well as E2f1 to the distal end of mouse Chromosome (Chr) 2 also suggests a close but unlinked genetic relationship between these cell cycle regulatory transcription factors.
Tài liệu tham khảo
Beijersbergen, R.L., Kerkhoven, R.M., Zhu, L., Cariée, L., Voorhoeve, P.M., Bernards, R. (1994a). E2F-4, a new member of the E2F gene family, has oncogenic activity and associates with p107 in vivo. Genes & Dev. 8, 2680–2690.
Beijersbergen, R.L., Hijmans, E.M., Zhu, L., Bernards, R. (1994b). Interaction of c-Myc with the pRb-related protein p107 results in inhibition of c-Myc-mediated transactivation. EMBO J. 13, 4080–4086.
Bhatia, K., Huppi, K., Spangler, G., Siwarski, D., Iyer, R., Magrath, I. (1993). Point mutations in the c-Myc transactivation domain are common in Burkitt’s lymphoma and mouse plasmacytomas. Nature Genet. 5, 56–61.
Bhatia, K., Spangler, G., Gaidano, G., Hamdy, N., Dalla-Favera, R., Magrath, I. (1994). Mutations in the coding region of c-myc occur frequently in acquired immunodeficiency syndrome-associated lymphomas. Blood 84, 883–888.
Clark, H.M., Yano, T., Otsuki, T., Jaffe, E.S., Shibata, D., Raffeid, M. (1994). Mutations in the coding region of c-MYC in AIDS-associated and other aggressive lymphomas. Cancer Res. 54, 3383–3386.
Ewen, M.E., Faha, B., Harlow, E., Livingston, D.M. (1992). Interaction of p107 with cyclin A independent of complex formation with viral oncoproteins. Science 255, 85–87.
Ewen, M.E., Xing, Y., Lawrence, J.B., Livingston, D.M. (1994). Molecular cloning, chromosomal mapping, and expression of the cDNA for p107, a retinoblastoma gene product-related protein. Cell 66, 1155–1164.
Faha, B., Ewen, M.E., Tsai, L.-H., Livingston, D.M., Harlow, E. (1992). Interaction between human cyclin A and adenovirus E1A-associated p107 protein. Science 255, 87–90.
Ginsberg, D., Vairo, G., Chittenden, T., Xiao, Z.-X., Xu, G., Wydner, K.L., DeCaprio, J.A., Lawrence, J.B., Livingston, D.M. (1994). E2F-4, a new member of the E2F transcription factor family, interacts with p107. Genes & Dev. 8, 2665–2679.
Gu, W., Bhatia, K., Magrath, I.T., Dang, C.V., Dalla-Favera, R. (1994). Binding and suppression of the Myc transcriptional activation domain by p107. Science 264, 251–254.
Hannon, G.J., Demetrick, D., Beach, D. (1993). Isolation of the Rb-related pl30 through its interaction with cdk2 and cyclins. Genes & Dev. 7, 2378–2391.
Hijmans, E.M., Voorhoeve, P.M., Beijersbergen, R.L., Van’t Veer, L.J., Bernards, R. (1995). E2F-5, a new E2F family member that interacts with pl30 in vivo. Mol. Cell. Biol. 15, 3082–3089.
Hinds, P.W., Mittnacht, S., Dulic, V., Arnold, A., Reed, S.I., Weinberg, R.A. (1992). Regulation of retinoblastoma protein functions by ectopic expression of human cyclins. Cell 70, 993–1006.
Huppi, K., Siwarski, D., Shaughnessy, J., Jr., Klemsz, M.J., Shirakata, M., Maki, R., Sakano, H. (1993). Genes associated with immunoglobulin V(D)J recombination are linked on mouse chromosome 2 and human chromosome 11. Immunogenetics 37, 288–291.
Kim, K.K., Soonpaa, M.H., Wang, H., Field, L.J. (1995). Developmental expression of pl07 mRNA and evidence for alternative splicing. Genomics 28, 520–529.
Lees, J.A., Saito, M., Vidal, M., Valentine, M., Look, T., Harlow, E., Dyson, N., Helin, K. (1993). Cyclin E/cdk2 and cyclin A/cdk2 kinases associate with pl07 and E2F in temporally distinct manner. Mol. Cell. Biol. 13, 7813–7825.
Li, Y., Graham, C, Lacy, S., Duncan, A.M.V., Whyte, P. (1993). The adenovirus Ela-associated 130-kD protein is encoded by a member of the retinoblastoma gene family and physically interacts with cyclins A and E. Genes & Dev. 7, 2366–2377.
Li, Y., Slansky, J.E., Myers, D.J., Drinkwater, N.R., Kaelin, W.G., Farnham, PJ. (1994). Cloning, chromosomal location and characterization of mouse E2F1. Mol. Cell. Biol. 14, 1861–1869.
Rustgi, A.K., Dyson, N., Bernards, R. (1991). The c-myc oncoprotein forms a specific complex with the product of the retinoblastoma gene. Nature 352, 541–544.
Sardet, C., Vidal, M., Cobrinik, D., Geng, Y., Onufryk, C., Chen, A., Weinberg, R.A. (1995). E2F-4 and E2F-5, two members of the E2F family, are expressed in the early phases of the cell cycle. Proc. Natl. Acad. Sci. USA 92, 2403–2407.
Siracusa, L.D., Abbott, C.M. (1994). Mouse Chromosome 2. Mamm. Genome 5 (suppl.), S22-S39.
Whyte, P., Williamson, N.M., Harlow, E. (1989). Cellular targets for transformation by the adenovirus E1A proteins. Cell 56, 67–75.
Yano, T., Sander, C.A., Clark, H.M., Dolezal, M.V., Jaffe, E.S., Raffeld, M. (1993). Clustered mutations in the second exon of the MYC gene in sporadic Burkitt’s lymphoma. Oncogene 8, 2741–2748.
Yee, S.P., Branton, P.E. (1985). Detection of cellular proteins associated with human adenovirus type 5 early region 1A polypeptides. Virology 147, 142–153.
Zhu, L., van den Heuvel, S., Helin, K., Fattaey, A., Ewen, M., Livingston, D., Dyson, N., Harlow, E. (1993). Inhibition of cell proliferation by p107, a relative of the retinoblastoma protein. Genes & Dev. 7, 1111–1125.
Zhu, L., Enders, G., Lees, J.A., Beijersbergen, R.L., Bernards, R., Harlow, E. (1995). The pRB-related protein pl07 contains two growth suppression domains: independent interactions with E2F and cyclin/cdk complexes. EMBO J. 14, 1904–1913.