Interference with the Expression of a Novel Human Polycomb Protein, hPc2, Results in Cellular Transformation and Apoptosis

作者: D P Satijn , D J Olson , J van der Vlag , K M Hamer , C Lambrechts

DOI: 10.1128/MCB.17.10.6076

关键词:

摘要: Polycomb (Pc) is involved in the stable and heritable repression of homeotic gene activity during Drosophila development. Here, we report identification a novel human Pc homolog, hPc2. This more closely related to Xenopus XPc, than previously described CBX2 (hPc1). However, hPc2 CBX2/hPc1 proteins colocalize interphase nuclei U-2 OS osteosarcoma cells, suggesting that are part common protein complex. To study functions generated mutant protein, DhPc2, which lacks an evolutionarily conserved C-terminal domain. domain important for function, since DhPc2 unable repress activity. Expression but not wild-type results cellular transformation mammalian cell lines as judged by phenotypic changes, altered marker expression, anchorage-independent growth. Specifically DhPc2-transformed expression c-myc proto-oncogene strongly enhanced serum deprivation apoptosis. In contrast, overexpression decreased expression. Our data suggest repressor interference with function can lead derepression transcription subsequently transformation. The member group (PcG) family. These genes memory system responsible inheritance progeny cells (7, 19, 21, 28, 38). Stable transmission crucial maintenance differentiated identity over many generations. It has been proposed PcG via formation multimeric complexes. model based on observation different proteins, including Pc, bind overlapping patterns polytene chromosomes salivary gland (32,

参考文章(48)
G Koopman, CP Reutelingsperger, GA Kuijten, RM Keehnen, ST Pals, MH van Oers, Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis. Blood. ,vol. 84, pp. 1415- 1420 ,(1994) , 10.1182/BLOOD.V84.5.1415.1415
A. Franke, M. DeCamillis, D. Zink, N. Cheng, H.W. Brock, R. Paro, Polycomb and polyhomeotic are constituents of a multimeric protein complex in chromatin of Drosophila melanogaster. The EMBO Journal. ,vol. 11, pp. 2941- 2950 ,(1992) , 10.1002/J.1460-2075.1992.TB05364.X
Stephen Subtelny, Paul B. Green, Developmental order, its origin and regulation A.R. Liss. ,(1982)
M Tagawa, T Sakamoto, K Shigemoto, H Matsubara, Y Tamura, T Ito, I Nakamura, A Okitsu, K Imai, M Taniguchi, Expression of novel DNA-binding protein with zinc finger structure in various tumor cells. Journal of Biological Chemistry. ,vol. 265, pp. 20021- 20026 ,(1990) , 10.1016/S0021-9258(17)45476-7
M. Kanno, M. Hasegawa, A. Ishida, K. Isono, M. Taniguchi, mel‐18, a Polycomb group‐related mammalian gene, encodes a transcriptional negative regulator with tumor suppressive activity. The EMBO Journal. ,vol. 14, pp. 5672- 5678 ,(1995) , 10.1002/J.1460-2075.1995.TB00254.X
Ian Duncan, E. B. Lewis, Genetic Control of Body Segment Differentiation in Drosophila Springer, Dordrecht. pp. 243- 261 ,(2007) , 10.1007/978-1-4020-6345-9_11
G I Evan, G K Lewis, G Ramsay, J M Bishop, Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product. Molecular and Cellular Biology. ,vol. 5, pp. 3610- 3616 ,(1985) , 10.1128/MCB.5.12.3610
J Stone, T de Lange, G Ramsay, E Jakobovits, J M Bishop, H Varmus, W Lee, Definition of regions in human c-myc that are involved in transformation and nuclear localization Molecular and Cellular Biology. ,vol. 7, pp. 1697- 1709 ,(1987) , 10.1128/MCB.7.5.1697