DREAM complex

The dimerization partner, RB-like, E2F and multi-vulval class B (DREAM) complex is a protein complex responsible for the regulation of cell cycle-dependent gene expression.[1] The complex is evolutionarily conserved, although some of its components vary from species to species. In humans, the key proteins in the complex are RBL1 (p107) and RBL2 (p130), both of which are homologs of RB (p105) and bind E2F transcription factors; E2F4 and E2F5 transcription factors which repress gene expression; DP1, DP2 and DP3, dimerization partners of E2F; and MuvB, which is a complex of LIN9/37/52/54 and RBBP4.[1]

Function

The main function of the DREAM complex is to repress gene expression during quiescence (G0). One of the genes repressed is the proto-oncogene Myc. Entry into G1 causes the dissociation of p130 from the complex, which prevents E2F4/5 from binding gene promoters. BMYB, which is repressed by the DREAM complex during G0 is expressed during G1 and it subsequently binds to MuvB during S phase to promote the expression of key G2/M phase genes such as CDK1 and CCNB1. FOXM1 is then recruited in G2 to further promote gene expression (e.g. AURKA). During late S phase BMYB is degraded via CUL1 (SCF complex), while FOXM1 is degraded during mitosis by the APC/C.[1][2] The DREAM complex regulates cytokinesis through GAS2L3.[3]

In Drosophila melanogaster there is a testis-specific paralog of the Myb-MuvB/DREAM complex known as tMAC (testis-specific meiotic arrest complex), which is involved in meiotic arrest.[4]

Apart from its role in cell cycle control, the DREAM complex has been shown to be involved in the programmed cell death of neural precursor cells in Drosophila melanogaster.[5]

Cancer therapy

Due to its regulatory role in the cell cycle, targeting the DREAM complex might enhance anticancer treatments such as imatinib.[6][7]

See also

References

  1. 1 2 3 Sadasivam, Subhashini; DeCaprio, James A. (11 July 2013). "The DREAM complex: master coordinator of cell cycle-dependent gene expression". Nature Reviews Cancer. 13 (8): 585–595. doi:10.1038/nrc3556.
  2. ↑ Sadasivam, S.; Duan, S.; DeCaprio, J. A. (5 March 2012). "The MuvB complex sequentially recruits B-Myb and FoxM1 to promote mitotic gene expression". Genes & Development. 26 (5): 474–489. doi:10.1101/gad.181933.111.
  3. ↑ Wolter, P; Schmitt, K; Fackler, M; Kremling, H; Probst, L; Hauser, S; Gruss, OJ; Gaubatz, S (15 May 2012). "GAS2L3, a target gene of the DREAM complex, is required for proper cytokinesis and genomic stability.". Journal of Cell Science. 125 (Pt 10): 2393–406. doi:10.1242/jcs.097253. PMID 22344256.
  4. ↑ Beall, E. L.; Lewis, P. W.; Bell, M.; Rocha, M.; Jones, D. L.; Botchan, M. R. (15 April 2007). "Discovery of tMAC: a Drosophila testis-specific meiotic arrest complex paralogous to Myb-Muv B". Genes & Development. 21 (8): 904–919. doi:10.1101/gad.1516607. PMC 1847709Freely accessible. PMID 17403774.
  5. ↑ Rovani, Margritte K.; Brachmann, Carrie Baker; Ramsay, Gary; Katzen, Alisa L. (December 2012). "The dREAM/Myb–MuvB complex and Grim are key regulators of the programmed death of neural precursor cells at the Drosophila posterior wing margin". Developmental Biology. 372 (1): 88–102. doi:10.1016/j.ydbio.2012.08.022.
  6. ↑ DeCaprio, James A.; Duensing, Anette (July 2014). "The DREAM complex in antitumor activity of imatinib mesylate in gastrointestinal stromal tumors". Current Opinion in Oncology. 26 (4): 415–421. doi:10.1097/CCO.0000000000000090.
  7. ↑ Boichuk, S.; Parry, J. A.; Makielski, K. R.; Litovchick, L.; Baron, J. L.; Zewe, J. P.; Wozniak, A.; Mehalek, K. R.; Korzeniewski, N.; Seneviratne, D. S.; Schoffski, P.; Debiec-Rychter, M.; DeCaprio, J. A.; Duensing, A. (20 June 2013). "The DREAM Complex Mediates GIST Cell Quiescence and Is a Novel Therapeutic Target to Enhance Imatinib-Induced Apoptosis". Cancer Research. 73 (16): 5120–5129. doi:10.1158/0008-5472.CAN-13-0579.

Further reading

This article is issued from Wikipedia - version of the 1/30/2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.