The protein encoded by this gene is a helix-loop-helix (HLH) protein that can form heterodimers with members of the basic HLH family of transcription factors.[1] The encoded protein has no DNA binding activity and therefore can inhibit the DNA binding and transcriptional activation ability of basic HLH proteins with which it interacts.[1] This protein may play a role in cell growth, senescence, and differentiation.[3][4][5] Two transcript variants encoding different isoforms have been found for this gene.[6]
Interactions
ID1 has been shown to interact weakly with MyoD[1][7][8][9][10][11][12] but very tightly with ubiquitously expressed E proteins.[13] E proteins heterodimerize with tissue restricted bHLH proteins such as Myod, NeuroD, etc. to form active transcription complexes so by sequestering E proteins, Id proteins can inhibit tissue restricted gene expression in multiple cell lineages using the same biochemical mechanism. Other interacting partners include CASK.[14]
↑ 1.01.11.21.3Benezra R, Davis RL, Lockshon D, Turner DL, Weintraub H (1990). "The protein Id: a negative regulator of helix-loop-helix DNA binding proteins". Cell. 61 (1): 49–59. doi:10.1016/0092-8674(90)90214-Y. PMID2156629.
↑Hara E, Yamaguchi T, Nojima H, Ide T, Campisi J, Okayama H, Oda K (February 1994). "Id-related genes encoding helix-loop-helix proteins are required for G1 progression and are repressed in senescent human fibroblasts". J Biol Chem. 269 (3): 2139–45. PMID8294468.
↑Perk J, Iavarone A, Benezra R (2005). "The Id family of helix-loop-helix proteins in cancer". Nat Rev Cancer. 5 (8): 603–614. doi:10.1038/nrc1673. PMID16034366.
↑Cunningham, Thomas J.; Yu, Michael S.; McKeithan, Wesley L.; Spiering, Sean; Carrette, Florent; Huang, Chun-Teng; Bushway, Paul J.; Tierney, Matthew; Albini, Sonia; Giacca, Mauro; Mano, Miguel; Puri, Pier Lorenzo; Sacco, Alessandra; Ruiz-Lozano, Pilar; Riou, Jean-Francois; Umbhauer, Muriel; Duester, Gregg; Mercola, Mark; Colas, Alexandre R. (1 July 2017). "Id genes are essential for early heart formation". Genes & Development. 31 (13): 1325–1338. doi:10.1101/gad.300400.117.
↑Garkavtsev I, Kozin SV, Chernova O, Xu L, Winkler F, Brown E, Barnett GH, Jain RK (March 2004). "The candidate tumour suppressor protein ING4 regulates brain tumour growth and angiogenesis". Nature. 428 (6980): 328–32. doi:10.1038/nature02329. PMID15029197.
↑Langlands K, Yin X, Anand G, Prochownik EV (August 1997). "Differential interactions of Id proteins with basic-helix-loop-helix transcription factors". J. Biol. Chem. 272 (32): 19785–93. doi:10.1074/jbc.272.32.19785. PMID9242638.
↑Finkel T, Duc J, Fearon ER, Dang CV, Tomaselli GF (January 1993). "Detection and modulation in vivo of helix-loop-helix protein-protein interactions". J. Biol. Chem. 268 (1): 5–8. PMID8380166.
↑Gupta K, Anand G, Yin X, Grove L, Prochownik EV (March 1998). "Mmip1: a novel leucine zipper protein that reverses the suppressive effects of Mad family members on c-myc". Oncogene. 16 (9): 1149–59. doi:10.1038/sj.onc.1201634. PMID9528857.
↑McLoughlin P, Ehler E, Carlile G, Licht JD, Schäfer BW (October 2002). "The LIM-only protein DRAL/FHL2 interacts with and is a corepressor for the promyelocytic leukemia zinc finger protein". J. Biol. Chem. 277 (40): 37045–53. doi:10.1074/jbc.M203336200. PMID12145280.
↑Ling MT, Chiu YT, Lee TK, Leung SC, Fung MK, Wang X, Wong KF, Wong YC (September 2008). "Id-1 induces proteasome-dependent degradation of the HBX protein". J. Mol. Biol. 382 (1): 34–43. doi:10.1016/j.jmb.2007.06.020. PMID18674781.
↑Jen Y, Weintraub H, Benezra R (August 1992). "Overexpression of Id protein inhibits the muscle differentiation program: in vivo association of Id with E2A proteins". Genes Dev. 6 (8): 1466–79. doi:10.1101/gad.6.8.1466. PMID1644289.
↑Qi J, Su Y, Sun R, Zhang F, Luo X, Yang Z, Luo X (March 2005). "CASK inhibits ECV304 cell growth and interacts with Id1". Biochem. Biophys. Res. Commun. 328 (2): 517–21. doi:10.1016/j.bbrc.2005.01.014. PMID15694377.
↑Lyden D, Young AZ, Zagzag D, Yan W, Gerald W, O'Reilly R, Bader BL, Hynes RO, Zhuang Y, Manova K, Benezra R (October 1999). "Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts". Nature. 401 (6754): 670–7. doi:10.1038/44334. PMID10537105.
↑Lyden D, Hattori K, Dias S, Costa C, Blaikie P, Butros L, Chadburn A, Heissig B, Marks W, Witte L, Wu Y, Hicklin D, Zhu Z, Hackett NR, Crystal RG, Moore MA, Hajjar KA, Manova K, Benezra R, Rafii S (November 2001). "Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth". Nat. Med. 7 (11): 1194–201. doi:10.1038/nm1101-1194. PMID11689883.
↑Henke E, Perk J, Vider J, de Candia P, Chin Y, Solit DB, Ponomarev V, Cartegni L, Manova K, Rosen N, Benezra R (January 2008). "Peptide-conjugated antisense oligonucleotides for targeted inhibition of a transcriptional regulator in vivo". Nat. Biotechnol. 26 (1): 91–100. doi:10.1038/nbt1366. PMID18176556.
Zhu W, Dahmen J, Bulfone A, Rigolet M, Hernandez MC, Kuo WL, Puelles L, Rubenstein JL, Israel MA (1995). "Id gene expression during development and molecular cloning of the human Id-1 gene". Brain Res. Mol. Brain Res. 30 (2): 312–26. doi:10.1016/0169-328X(95)00017-M. PMID7637581.
Deed RW, Jasiok M, Norton JD (1994). "Nucleotide sequence of the cDNA encoding human helix-loop-helix Id-1 protein: identification of functionally conserved residues common to Id proteins". Biochim. Biophys. Acta. 1219 (1): 160–2. doi:10.1016/0167-4781(94)90261-5. PMID8086456.
Mathew S, Chen W, Murty VV, Benezra R, Chaganti RS (1996). "Chromosomal assignment of human ID1 and ID2 genes". Genomics. 30 (2): 385–7. doi:10.1006/geno.1995.0037. PMID8586447.
Nehlin JO, Hara E, Kuo WL, Collins C, Campisi J (1997). "Genomic organization, sequence, and chromosomal localization of the human helix-loop-helix Id1 gene". Biochem. Biophys. Res. Commun. 231 (3): 628–34. doi:10.1006/bbrc.1997.6152. PMID9070860.
Anand G, Yin X, Shahidi AK, Grove L, Prochownik EV (1997). "Novel regulation of the helix-loop-helix protein Id1 by S5a, a subunit of the 26 S proteasome". J. Biol. Chem. 272 (31): 19140–51. doi:10.1074/jbc.272.31.19140. PMID9235903.
Langlands K, Yin X, Anand G, Prochownik EV (1997). "Differential interactions of Id proteins with basic-helix-loop-helix transcription factors". J. Biol. Chem. 272 (32): 19785–19793. doi:10.1074/jbc.272.32.19785. PMID9242638.
Outinen PA, Sood SK, Pfeifer SI, Pamidi S, Podor TJ, Li J, Weitz JI, Austin RC (1999). "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. PMID10419887.
Langlands K, Down GA, Kealey T (2000). "Id proteins are dynamically expressed in normal epidermis and dysregulated in squamous cell carcinoma". Cancer Res. 60 (21): 5929–33. PMID11085505.
Ohtani N, Zebedee Z, Huot TJ, Stinson JA, Sugimoto M, Ohashi Y, Sharrocks AD, Peters G, Hara E (2001). "Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence". Nature. 409 (6823): 1067–70. doi:10.1038/35059131. PMID11234019.
Korchynskyi O, ten Dijke P (2002). "Identification and functional characterization of distinct critically important bone morphogenetic protein-specific response elements in the Id1 promoter". J. Biol. Chem. 277 (7): 4883–4891. doi:10.1074/jbc.M111023200. PMID11729207.
Jögi A, Persson P, Grynfeld A, Påhlman S, Axelson H (2002). "Modulation of basic helix-loop-helix transcription complex formation by Id proteins during neuronal differentiation". J. Biol. Chem. 277 (11): 9118–26. doi:10.1074/jbc.M107713200. PMID11756408.
Singh J, Murata K, Itahana Y, Desprez PY (2002). "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): 1812–1822. doi:10.1038/sj.onc.1205252. PMID11896613.
Ouyang XS, Wang X, Ling MT, Wong HL, Tsao SW, Wong YC (2002). "Id-1 stimulates serum independent prostate cancer cell proliferation through inactivation of p16(INK4a)/pRB pathway". Carcinogenesis. 23 (5): 721–5. doi:10.1093/carcin/23.5.721. PMID12016143.
Ling MT, Wang X, Tsao SW, Wong YC (2002). "Down-regulation of Id-1 expression is associated with TGF beta 1-induced growth arrest in prostate epithelial cells". Biochim. Biophys. Acta. 1570 (3): 145–52. doi:10.1016/S0304-4165(02)00189-7. PMID12020803.
Wang X, Xu K, Ling MT, Wong YC, Feng HC, Nicholls J, Tsao SW (2002). "Evidence of increased Id-1 expression and its role in cell proliferation in nasopharyngeal carcinoma cells". Mol. Carcinog. 35 (1): 42–9. doi:10.1002/mc.10072. PMID12203366.