SPEN explained

Msx2-interacting protein is a protein that in humans is encoded by the SPEN gene.^{[1] [2] [3]}

This gene encodes a hormone inducible transcriptional repressor. Repression of transcription by this gene product can occur through interactions with other repressors, by the recruitment of proteins involved in histone deacetylation, or through sequestration of transcriptional activators. The product of this gene contains a carboxy-terminal domain that permits binding to other corepressor proteins. This domain also permits interaction with members of the NuRD complex, a nucleosome remodeling protein complex that contains deacetylase activity. In addition, this repressor contains several RNA recognition motifs that confer binding to a steroid receptor RNA coactivator; this binding can modulate the activity of both liganded and nonliganded steroid receptors.^[4]

Interactions

SPEN has been shown to interact with HDAC1, SRA1^[2] and Nuclear receptor co-repressor 2.^[2]

Further reading

• Ternovskaia LN, Prokhorova LG, Moroz VM . [Antagonistic interrelationships between the staphylococci and Sarcina isolated from the upper respiratory tracts of virtually healthy persons] . Antibiotiki . 21 . 12 . 1072–5 . 1977 . 1020939 .
• Nagase T, Ishikawa K, Suyama M, etal . Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. . DNA Res. . 6 . 1 . 63–70 . 1999 . 10231032 . 10.1093/dnares/6.1.63 . free .
• Shi Y, Hon M, Evans RM . The peroxisome proliferator-activated receptor delta, an integrator of transcriptional repression and nuclear receptor signaling. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 5 . 2613–8 . 2002 . 11867749 . 10.1073/pnas.052707099 . 122396 . 2002PNAS...99.2613S . free .
• Oswald F, Kostezka U, Astrahantseff K, etal . SHARP is a novel component of the Notch/RBP-Jkappa signalling pathway. . EMBO J. . 21 . 20 . 5417–26 . 2002 . 12374742 . 10.1093/emboj/cdf549 . 129081 .
• Ariyoshi M, Schwabe JW . A conserved structural motif reveals the essential transcriptional repression function of Spen proteins and their role in developmental signaling. . Genes Dev. . 17 . 15 . 1909–20 . 2003 . 12897056 . 10.1101/gad.266203 . 196244 .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Dotzlaw H, Papaioannou M, Moehren U, etal . Agonist-antagonist induced coactivator and corepressor interplay on the human androgen receptor. . Mol. Cell. Endocrinol. . 213 . 1 . 79–85 . 2004 . 15062576 . 10.1016/j.mce.2003.10.036 . 46437905 .
• Beausoleil SA, Jedrychowski M, Schwartz D, etal . Large-scale characterization of HeLa cell nuclear phosphoproteins. . Proc. Natl. Acad. Sci. U.S.A. . 101 . 33 . 12130–5 . 2004 . 15302935 . 10.1073/pnas.0404720101 . 514446 . 2004PNAS..10112130B . free .
• Vadlamudi RK, Manavathi B, Singh RR, etal . An essential role of Pak1 phosphorylation of SHARP in Notch signaling. . Oncogene . 24 . 28 . 4591–6 . 2005 . 15824732 . 10.1038/sj.onc.1208672 . free .
• Li J, Wang J, Yang X, etal . The Spen homolog Msx2-interacting nuclear target protein interacts with the E2 ubiquitin-conjugating enzyme UbcH8. . Mol. Cell. Biochem. . 288 . 1–2 . 151–7 . 2007 . 16583136 . 10.1007/s11010-006-9131-9 . 24935755 .
• Gregory SG, Barlow KF, McLay KE, etal . The DNA sequence and biological annotation of human chromosome 1. . Nature . 441 . 7091 . 315–21 . 2006 . 16710414 . 10.1038/nature04727 . 2006Natur.441..315G . free .
• Lim J, Hao T, Shaw C, etal . A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. . Cell . 125 . 4 . 801–14 . 2006 . 16713569 . 10.1016/j.cell.2006.03.032 . 13709685 . free .
• Beausoleil SA, Villén J, Gerber SA, etal . A probability-based approach for high-throughput protein phosphorylation analysis and site localization. . Nat. Biotechnol. . 24 . 10 . 1285–92 . 2006 . 16964243 . 10.1038/nbt1240 . 14294292 .
• Olsen JV, Blagoev B, Gnad F, etal . Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. . Cell . 127 . 3 . 635–48 . 2006 . 17081983 . 10.1016/j.cell.2006.09.026 . 7827573 . free .
• Feng Y, Bommer GT, Zhai Y, etal . Drosophila split ends homologue SHARP functions as a positive regulator of Wnt/beta-catenin/T-cell factor signaling in neoplastic transformation. . Cancer Res. . 67 . 2 . 482–91 . 2007 . 17234755 . 10.1158/0008-5472.CAN-06-2314 . free .

Notes and References

1. Newberry EP, Latifi T, Towler DA . The RRM domain of MINT, a novel Msx2 binding protein, recognizes and regulates the rat osteocalcin promoter . Biochemistry . 38 . 33 . 10678–90 . Sep 1999 . 10451362 . 10.1021/bi990967j .
2. Shi Y, Downes M, Xie W, Kao HY, Ordentlich P, Tsai CC, Hon M, Evans RM . Sharp, an inducible cofactor that integrates nuclear receptor repression and activation . Genes Dev . 15 . 9 . 1140–51 . May 2001 . 11331609 . 312688 . 10.1101/gad.871201 .
3. Web site: Entrez Gene: SPEN spen homolog, transcriptional regulator (Drosophila).
4. Web site: Entrez Gene: SPEN spen homolog, transcriptional regulator (Drosophila).