ID1
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ID1（inhibitor of DNA binding 1）は、ヒトではID1遺伝子によってコードされているタンパク質である[1][2]。
機能
ID1タンパク質はヘリックスループヘリックス（HLH）タンパク質であり、塩基性ヘリックスループヘリックス（bHLH）ファミリーの転写因子とヘテロ二量体を形成することができる[1]。ID1はDNA結合活性を持たないため、相互作用するbHLHタンパク質のDNA結合と転写活性化作用を阻害する[1]。このタンパク質は、細胞成長、老化、そして分化に関与している可能性がある[3][4][5]。
相互作用
ID1はMyoDと弱く相互作用することが示されているが[1][6][7][8][9][10][11]、E2A遺伝子にコードされ普遍的に発現しているEタンパク質と極めて強固に結合する[12]。Eタンパク質はMyoDやNeuroDといった組織限定型bHLHタンパク質とヘテロ二量体を形成して活性型転写因子複合体を形成する。そのため、IDタンパク質はEタンパク質を隔離することで、複数の細胞系統において同一の生化学的機構によって組織限定型の遺伝子発現を阻害する。ID1の他の相互作用パートナーとしてはCASKが知られている[13]。
臨床的意義
ID1は、腫瘍の成長や血管新生に重要な血管内皮前駆細胞を標識するために利用される[14][15]。また、ID1を標的化して阻害することによって腫瘍の成長が低下する[16][17]。ID1は特定種の神経膠腫や乳がんにおいてカンナビジオールによって標的化されることが示されている[18][19]。
出典
- 1 2 3 4 “The protein Id: a negative regulator of helix-loop-helix DNA binding proteins”. Cell 61 (1): 49–59. (April 1990). doi:10.1016/0092-8674(90)90214-Y. PMID 2156629.
- ↑ “Id-related genes encoding helix-loop-helix proteins are required for G1 progression and are repressed in senescent human fibroblasts”. The Journal of Biological Chemistry 269 (3): 2139–45. (January 1994). doi:10.1016/S0021-9258(17)42146-6. PMID 8294468.
- ↑ “Id proteins in development, cell cycle and cancer”. Trends in Cell Biology 13 (8): 410–8. (August 2003). doi:10.1016/S0962-8924(03)00147-8. PMID 12888293.
- ↑ “Id family of helix-loop-helix proteins in cancer”. Nature Reviews. Cancer 5 (8): 603–14. (August 2005). doi:10.1038/nrc1673. PMID 16034366.
- ↑ Cunningham, Thomas J.; Yu, Michael S.; McKeithan, Wesley L.; Spiering, Sean; Carrette, Florent; Huang, Chun-Teng; Bushway, Paul J.; Tierney, Matthew et al. (2017-07-01). “Id genes are essential for early heart formation”. Genes & Development 31 (13): 1325–1338. doi:10.1101/gad.300400.117. ISSN 1549-5477. PMC 5580654. PMID 28794185.
- ↑ “The candidate tumour suppressor protein ING4 regulates brain tumour growth and angiogenesis”. Nature 428 (6980): 328–32. (March 2004). Bibcode: 2004Natur.428..328G. doi:10.1038/nature02329. PMID 15029197.
- ↑ “Differential interactions of Id proteins with basic-helix-loop-helix transcription factors”. The Journal of Biological Chemistry 272 (32): 19785–93. (August 1997). doi:10.1074/jbc.272.32.19785. PMID 9242638.
- ↑ “Detection and modulation in vivo of helix-loop-helix protein-protein interactions”. The Journal of Biological Chemistry 268 (1): 5–8. (January 1993). doi:10.1016/S0021-9258(18)54105-3. PMID 8380166.
- ↑ “Mmip1: a novel leucine zipper protein that reverses the suppressive effects of Mad family members on c-myc”. Oncogene 16 (9): 1149–59. (March 1998). doi:10.1038/sj.onc.1201634. PMID 9528857.
- ↑ “The LIM-only protein DRAL/FHL2 interacts with and is a corepressor for the promyelocytic leukemia zinc finger protein”. The Journal of Biological Chemistry 277 (40): 37045–53. (October 2002). doi:10.1074/jbc.M203336200. PMID 12145280.
- ↑ “Id-1 induces proteasome-dependent degradation of the HBX protein”. Journal of Molecular Biology 382 (1): 34–43. (September 2008). doi:10.1016/j.jmb.2007.06.020. PMID 18674781.
- ↑ “Overexpression of Id protein inhibits the muscle differentiation program: in vivo association of Id with E2A proteins”. Genes & Development 6 (8): 1466–79. (August 1992). doi:10.1101/gad.6.8.1466. PMID 1644289.
- ↑ “CASK inhibits ECV304 cell growth and interacts with Id1”. Biochemical and Biophysical Research Communications 328 (2): 517–21. (March 2005). doi:10.1016/j.bbrc.2005.01.014. PMID 15694377.
- ↑ “Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts”. Nature 401 (6754): 670–7. (October 1999). Bibcode: 1999Natur.401..670L. doi:10.1038/44334. PMID 10537105.
- ↑ “Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth”. Nature Medicine 7 (11): 1194–201. (November 2001). doi:10.1038/nm1101-1194. PMID 11689883.
- ↑ “Peptide-conjugated antisense oligonucleotides for targeted inhibition of a transcriptional regulator in vivo”. Nature Biotechnology 26 (1): 91–100. (January 2008). doi:10.1038/nbt1366. PMID 18176556.
- ↑ “Using the transcription factor inhibitor of DNA binding 1 to selectively target endothelial progenitor cells offers novel strategies to inhibit tumor angiogenesis and growth”. Cancer Research 70 (18): 7273–82. (September 2010). doi:10.1158/0008-5472.CAN-10-1142. PMC 3058751. PMID 20807818.
- ↑ “Therapeutic reversal of prenatal pontine ID1 signaling in DIPG”. Neuro Oncol 23 (supplement 1): i48. (June 2021). doi:10.1093/neuonc/noab090.193. PMC 8168201.
- ↑ “Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells”. Molecular Cancer Therapeutics 6 (11): 2921–7. (November 2007). doi:10.1158/1535-7163.MCT-07-0371. PMID 18025276.
関連文献
- “Id gene expression during development and molecular cloning of the human Id-1 gene”. Brain Research. Molecular Brain Research 30 (2): 312–26. (June 1995). doi:10.1016/0169-328X(95)00017-M. PMID 7637581.
- “Nucleotide sequence of the cDNA encoding human helix-loop-helix Id-1 protein: identification of functionally conserved residues common to Id proteins”. Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression 1219 (1): 160–2. (September 1994). doi:10.1016/0167-4781(94)90261-5. PMID 8086456.
- “Chromosomal assignment of human ID1 and ID2 genes”. Genomics 30 (2): 385–7. (November 1995). doi:10.1006/geno.1995.0037. PMID 8586447.
- “Genomic organization, sequence, and chromosomal localization of the human helix-loop-helix Id1 gene”. Biochemical and Biophysical Research Communications 231 (3): 628–34. (February 1997). doi:10.1006/bbrc.1997.6152. PMID 9070860.
- “Novel regulation of the helix-loop-helix protein Id1 by S5a, a subunit of the 26 S proteasome”. The Journal of Biological Chemistry 272 (31): 19140–51. (August 1997). doi:10.1074/jbc.272.31.19140. PMID 9235903.
- “Differential interactions of Id proteins with basic-helix-loop-helix transcription factors”. The Journal of Biological Chemistry 272 (32): 19785–93. (August 1997). doi:10.1074/jbc.272.32.19785. PMID 9242638.
- “Id helix-loop-helix proteins inhibit nucleoprotein complex formation by the TCF ETS-domain transcription factors”. The EMBO Journal 18 (4): 968–76. (February 1999). doi:10.1093/emboj/18.4.968. PMC 1171189. PMID 10022839.
- “Homocysteine-induced endoplasmic reticulum stress and growth arrest leads to specific changes in gene expression in human vascular endothelial cells”. Blood 94 (3): 959–67. (August 1999). doi:10.1182/blood.V94.3.959.415k20_959_967. PMID 10419887.
- “Id proteins are dynamically expressed in normal epidermis and dysregulated in squamous cell carcinoma”. Cancer Research 60 (21): 5929–33. (November 2000). PMID 11085505.
- “Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence”. Nature 409 (6823): 1067–70. (February 2001). Bibcode: 2001Natur.409.1067O. doi:10.1038/35059131. PMID 11234019.
- “Protein-protein interaction panel using mouse full-length cDNAs”. Genome Research 11 (10): 1758–65. (October 2001). doi:10.1101/gr.180101. PMC 311163. PMID 11591653.
- “Identification and functional characterization of distinct critically important bone morphogenetic protein-specific response elements in the Id1 promoter”. The Journal of Biological Chemistry 277 (7): 4883–91. (February 2002). doi:10.1074/jbc.M111023200. PMID 11729207.
- “Modulation of basic helix-loop-helix transcription complex formation by Id proteins during neuronal differentiation”. The Journal of Biological Chemistry 277 (11): 9118–26. (March 2002). doi:10.1074/jbc.M107713200. PMID 11756408.
- “Constitutive expression of the Id-1 promoter in human metastatic breast cancer cells is linked with the loss of NF-1/Rb/HDAC-1 transcription repressor complex”. Oncogene 21 (12): 1812–22. (March 2002). doi:10.1038/sj.onc.1205252. PMID 11896613.
- “The MyoD-inducible p204 protein overcomes the inhibition of myoblast differentiation by Id proteins”. Molecular and Cellular Biology 22 (9): 2893–905. (May 2002). doi:10.1128/MCB.22.9.2893-2905.2002. PMC 133750. PMID 11940648.
- “Id-1 stimulates serum independent prostate cancer cell proliferation through inactivation of p16(INK4a)/pRB pathway”. Carcinogenesis 23 (5): 721–5. (May 2002). doi:10.1093/carcin/23.5.721. PMID 12016143.
- “Down-regulation of Id-1 expression is associated with TGF beta 1-induced growth arrest in prostate epithelial cells”. Biochimica et Biophysica Acta (BBA) - General Subjects 1570 (3): 145–52. (April 2002). doi:10.1016/S0304-4165(02)00189-7. PMID 12020803.
- “Evidence of increased Id-1 expression and its role in cell proliferation in nasopharyngeal carcinoma cells”. Molecular Carcinogenesis 35 (1): 42–9. (September 2002). doi:10.1002/mc.10072. PMID 12203366.
関連項目
外部リンク
- ID1 protein, human - MeSH・アメリカ国立医学図書館・生命科学用語シソーラス
- Overview of all the structural information available in the PDB for UniProt: P20067 (Mouse DNA-binding protein inhibitor ID-1) at the PDBe-KB.