DRAP1 explained

Dr1-associated corepressor is a protein that in humans is encoded by the DRAP1 gene.^{[1] [2]}

Transcriptional repression is a general mechanism for regulating transcriptional initiation in organisms ranging from yeast to humans. Accurate initiation of transcription from eukaryotic protein-encoding genes requires the assembly of a large multiprotein complex consisting of RNA polymerase II and general transcription factors such as TFIIA, TFIIB, and TFIID. DR1 is a repressor that interacts with the TATA-binding protein (TBP) of TFIID and prevents the formation of an active transcription complex by precluding the entry of TFIIA and/or TFIIB into the preinitiation complex. The protein encoded by this gene is a corepressor of transcription that interacts with DR1 to enhance DR1-mediated repression. The interaction between this corepressor and DR1 is required for corepressor function and appears to stabilize the TBP-DR1-DNA complex.^[2]

Interactions

DRAP1 has been shown to interact with FOXH1^[3] and DR1.^{[4] [5]}

Further reading

• Goppelt A, Stelzer G, Lottspeich F, Meisterernst M . A mechanism for repression of class II gene transcription through specific binding of NC2 to TBP-promoter complexes via heterodimeric histone fold domains . The EMBO Journal . 15 . 12 . 3105–16 . June 1996 . 8670811 . 450253 . 10.1002/j.1460-2075.1996.tb00673.x .
• Yeung K, Kim S, Reinberg D . Functional dissection of a human Dr1-DRAP1 repressor complex . Molecular and Cellular Biology . 17 . 1 . 36–45 . January 1997 . 8972183 . 231727 . 10.1128/MCB.17.1.36 .
• Ikeda K, Halle JP, Stelzer G, Meisterernst M, Kawakami K . Involvement of negative cofactor NC2 in active repression by zinc finger-homeodomain transcription factor AREB6 . Molecular and Cellular Biology . 18 . 1 . 10–8 . January 1998 . 9418848 . 121442 . 10.1128/mcb.18.1.10 .
• Castaño E, Gross P, Wang Z, Roeder RG, Oelgeschläger T . The C-terminal domain-phosphorylated IIO form of RNA polymerase II is associated with the transcription repressor NC2 (Dr1/DRAP1) and is required for transcription activation in human nuclear extracts . Proceedings of the National Academy of Sciences of the United States of America . 97 . 13 . 7184–9 . June 2000 . 10852970 . 16520 . 10.1073/pnas.140202297 . 2000PNAS...97.7184C . free .
• Kamada K, Shu F, Chen H, Malik S, Stelzer G, Roeder RG, Meisterernst M, Burley SK . 6 . Crystal structure of negative cofactor 2 recognizing the TBP-DNA transcription complex . Cell . 106 . 1 . 71–81 . July 2001 . 11461703 . 10.1016/S0092-8674(01)00417-2 . 11064090 . free .
• Iratni R, Yan YT, Chen C, Ding J, Zhang Y, Price SM, Reinberg D, Shen MM . 6 . Inhibition of excess nodal signaling during mouse gastrulation by the transcriptional corepressor DRAP1 . Science . 298 . 5600 . 1996–9 . December 2002 . 12471260 . 10.1126/science.1073405 . 2002Sci...298.1996I . 22923124 .
• Denko N, Wernke-Dollries K, Johnson AB, Hammond E, Chiang CM, Barton MC . Hypoxia actively represses transcription by inducing negative cofactor 2 (Dr1/DrAP1) and blocking preinitiation complex assembly . The Journal of Biological Chemistry . 278 . 8 . 5744–9 . February 2003 . 12477712 . 10.1074/jbc.M212534200 . free .
• Leonard D, Ajuh P, Lamond AI, Legerski RJ . hLodestar/HuF2 interacts with CDC5L and is involved in pre-mRNA splicing . Biochemical and Biophysical Research Communications . 308 . 4 . 793–801 . September 2003 . 12927788 . 10.1016/S0006-291X(03)01486-4 . 10.1.1.539.8359 .
• Klejman MP, Pereira LA, van Zeeburg HJ, Gilfillan S, Meisterernst M, Timmers HT . NC2alpha interacts with BTAF1 and stimulates its ATP-dependent association with TATA-binding protein . Molecular and Cellular Biology . 24 . 22 . 10072–82 . November 2004 . 15509807 . 525489 . 10.1128/MCB.24.22.10072-10082.2004 .
• Lewis BA, Sims RJ, Lane WS, Reinberg D . Functional characterization of core promoter elements: DPE-specific transcription requires the protein kinase CK2 and the PC4 coactivator . Molecular Cell . 18 . 4 . 471–81 . May 2005 . 15893730 . 10.1016/j.molcel.2005.04.005 . free .
• Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE . 6 . A human protein-protein interaction network: a resource for annotating the proteome . Cell . 122 . 6 . 957–68 . September 2005 . 16169070 . 10.1016/j.cell.2005.08.029 . 11858/00-001M-0000-0010-8592-0 . 8235923 . free .
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . 6 . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . October 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Assmann EM, Alborghetti MR, Camargo ME, Kobarg J . FEZ1 dimerization and interaction with transcription regulatory proteins involves its coiled-coil region . The Journal of Biological Chemistry . 281 . 15 . 9869–81 . April 2006 . 16484223 . 10.1074/jbc.M513280200 . free .
• Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY . 6 . A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration . Cell . 125 . 4 . 801–14 . May 2006 . 16713569 . 10.1016/j.cell.2006.03.032 . 13709685 . free .
• Albert TK, Grote K, Boeing S, Stelzer G, Schepers A, Meisterernst M . Global distribution of negative cofactor 2 subunit-alpha on human promoters . Proceedings of the National Academy of Sciences of the United States of America . 104 . 24 . 10000–5 . June 2007 . 17548813 . 1891239 . 10.1073/pnas.0703490104 . 2007PNAS..10410000A . free .

Notes and References

1. Mermelstein F, Yeung K, Cao J, Inostroza JA, Erdjument-Bromage H, Eagelson K, Landsman D, Levitt P, Tempst P, Reinberg D . 6 . Requirement of a corepressor for Dr1-mediated repression of transcription . Genes & Development . 10 . 8 . 1033–48 . April 1996 . 8608938 . 10.1101/gad.10.8.1033 . free .
2. Web site: Entrez Gene: DRAP1 DR1-associated protein 1 (negative cofactor 2 alpha).
3. Iratni R, Yan YT, Chen C, Ding J, Zhang Y, Price SM, Reinberg D, Shen MM . 6 . Inhibition of excess nodal signaling during mouse gastrulation by the transcriptional corepressor DRAP1 . Science . 298 . 5600 . 1996–9 . December 2002 . 12471260 . 10.1126/science.1073405 . 2002Sci...298.1996I . 22923124 .
4. Mermelstein F, Yeung K, Cao J, Inostroza JA, Erdjument-Bromage H, Eagelson K, Landsman D, Levitt P, Tempst P, Reinberg D . 6 . Requirement of a corepressor for Dr1-mediated repression of transcription . Genes & Development . 10 . 8 . 1033–48 . April 1996 . 8608938 . 10.1101/gad.10.8.1033 . free .
5. Yeung K, Kim S, Reinberg D . Functional dissection of a human Dr1-DRAP1 repressor complex . Molecular and Cellular Biology . 17 . 1 . 36–45 . January 1997 . 8972183 . 231727 . 10.1128/MCB.17.1.36 .