LIM domain only 2 (rhombotin-like 1), also known as LMO2, RBTNL1, RBTN2, RHOM2, LIM Domain Only Protein 2, TTG2, and T-Cell Translocation Protein 2, is a protein which in humans is encoded by the LMO2gene.[5]
LMO2 encodes a cysteine-rich, two LIM domain protein that is required for yolk sac erythropoiesis.[6] The LMO2 protein has a central and crucial role in hematopoietic development and is highly conserved.
Aberrant LMO2 expression is a significant feature of T cell acute lymphoblastic leukaemia with multiple described mechanisms of activation.[5][7] The LMO2 transcription start site is located approximately 25 kb downstream from the 11p13 T-cell translocation cluster (11p13 ttc), where a number of T-cell acute lymphoblastic leukemia-specific translocations occur.[8] An upstream noncoding DNA element is also the site of recurrent mutations in T cell acute lymphoblastic leukaemia, leading the recruitment of the transcription factor MYB and significant H3K27ac enrichment and thus the formation of an aberrant enhancer which up-regulates the expression of LMO2[9] Furthermore, recurrent and somatically acquired mutations of LMO2intron 1 lead to its over-expression in both adult and paediatric T cell acute lymphoblastic leukaemia.[10] These mutations introduce new transcription factor binding sites for MYB, ETS1 and RUNX1 allowing for the formation of an aberrant promoter which drives LMO2 expression.
^Rahman S, Magnussen M, León TE, Farah N, Li Z, Abraham BJ, et al. (June 2017). "Activation of the LMO2 oncogene through a somatically acquired neomorphic promoter in T-cell acute lymphoblastic leukemia". Blood. 129 (24): 3221–3226. doi:10.1182/blood-2016-09-742148. PMC5472898. PMID28270453.3221-3226&rft.date=2017-06&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472898#id-name=PMC&rft_id=info:pmid/28270453&rft_id=info:doi/10.1182/blood-2016-09-742148&rft.aulast=Rahman&rft.aufirst=S&rft.au=Magnussen, M&rft.au=León, TE&rft.au=Farah, N&rft.au=Li, Z&rft.au=Abraham, BJ&rft.au=Alapi, KZ&rft.au=Mitchell, RJ&rft.au=Naughton, T&rft.au=Fielding, AK&rft.au=Pizzey, A&rft.au=Bustraan, S&rft.au=Allen, C&rft.au=Popa, T&rft.au=Pike-Overzet, K&rft.au=Garcia-Perez, L&rft.au=Gale, RE&rft.au=Linch, DC&rft.au=Staal, FJ&rft.au=Young, RA&rft.au=Look, AT&rft.au=Mansour, MR&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472898&rfr_id=info:sid/en.wikipedia.org:LMO2" class="Z3988">
^ abcOsada H, Grutz G, Axelson H, Forster A, Rabbitts TH (October 1995). "Association of erythroid transcription factors: complexes involving the LIM protein RBTN2 and the zinc-finger protein GATA1". Proceedings of the National Academy of Sciences of the United States of America. 92 (21): 9585–9589. Bibcode:1995PNAS...92.9585O. doi:10.1073/pnas.92.21.9585. PMC40846. PMID7568177.9585-9589&rft.date=1995-10&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC40846#id-name=PMC&rft_id=info:pmid/7568177&rft_id=info:doi/10.1073/pnas.92.21.9585&rft_id=info:bibcode/1995PNAS...92.9585O&rft.aulast=Osada&rft.aufirst=H&rft.au=Grutz, G&rft.au=Axelson, H&rft.au=Forster, A&rft.au=Rabbitts, TH&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC40846&rfr_id=info:sid/en.wikipedia.org:LMO2" class="Z3988">
^Bégay-Müller V, Ansieau S, Leutz A (June 2002). "The LIM domain protein Lmo2 binds to AF6, a translocation partner of the MLL oncogene". FEBS Letters. 521 (1–3): 36–38. Bibcode:2002FEBSL.521...36B. doi:10.1016/s0014-5793(02)02814-4. PMID12067721. S2CID29461336.1–3&rft.pages=36-38&rft.date=2002-06&rft_id=info:doi/10.1016/s0014-5793(02)02814-4&rft_id=https://api.semanticscholar.org/CorpusID:29461336#id-name=S2CID&rft_id=info:pmid/12067721&rft_id=info:bibcode/2002FEBSL.521...36B&rft.aulast=Bégay-Müller&rft.aufirst=V&rft.au=Ansieau, S&rft.au=Leutz, A&rfr_id=info:sid/en.wikipedia.org:LMO2" class="Z3988">
^Wadman I, Li J, Bash RO, Forster A, Osada H, Rabbitts TH, Baer R (October 1994). "Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukemia". The EMBO Journal. 13 (20): 4831–4839. doi:10.1002/j.1460-2075.1994.tb06809.x. PMC395422. PMID7957052.4831-4839&rft.date=1994-10&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC395422#id-name=PMC&rft_id=info:pmid/7957052&rft_id=info:doi/10.1002/j.1460-2075.1994.tb06809.x&rft.aulast=Wadman&rft.aufirst=I&rft.au=Li, J&rft.au=Bash, RO&rft.au=Forster, A&rft.au=Osada, H&rft.au=Rabbitts, TH&rft.au=Baer, R&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC395422&rfr_id=info:sid/en.wikipedia.org:LMO2" class="Z3988">
^Valge-Archer VE, Osada H, Warren AJ, Forster A, Li J, Baer R, Rabbitts TH (August 1994). "The LIM protein RBTN2 and the basic helix-loop-helix protein TAL1 are present in a complex in erythroid cells". Proceedings of the National Academy of Sciences of the United States of America. 91 (18): 8617–8621. Bibcode:1994PNAS...91.8617V. doi:10.1073/pnas.91.18.8617. PMC44657. PMID8078932.8617-8621&rft.date=1994-08&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC44657#id-name=PMC&rft_id=info:pmid/8078932&rft_id=info:doi/10.1073/pnas.91.18.8617&rft_id=info:bibcode/1994PNAS...91.8617V&rft.aulast=Valge-Archer&rft.aufirst=VE&rft.au=Osada, H&rft.au=Warren, AJ&rft.au=Forster, A&rft.au=Li, J&rft.au=Baer, R&rft.au=Rabbitts, TH&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC44657&rfr_id=info:sid/en.wikipedia.org:LMO2" class="Z3988">
^Goardon N, Lambert JA, Rodriguez P, Nissaire P, Herblot S, Thibault P, et al. (January 2006). "ETO2 coordinates cellular proliferation and differentiation during erythropoiesis". The EMBO Journal. 25 (2): 357–366. doi:10.1038/sj.emboj.7600934. PMC1383517. PMID16407974.357-366&rft.date=2006-01&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1383517#id-name=PMC&rft_id=info:pmid/16407974&rft_id=info:doi/10.1038/sj.emboj.7600934&rft.aulast=Goardon&rft.aufirst=N&rft.au=Lambert, JA&rft.au=Rodriguez, P&rft.au=Nissaire, P&rft.au=Herblot, S&rft.au=Thibault, P&rft.au=Dumenil, D&rft.au=Strouboulis, J&rft.au=Romeo, PH&rft.au=Hoang, T&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1383517&rfr_id=info:sid/en.wikipedia.org:LMO2" class="Z3988">
Royer-Pokora B, Loos U, Ludwig WD (October 1991). "TTG-2, a new gene encoding a cysteine-rich protein with the LIM motif, is overexpressed in acute T-cell leukaemia with the t(11;14)(p13;q11)". Oncogene. 6 (10): 1887–1893. PMID1923511.1887-1893&rft.date=1991-10&rft_id=info:pmid/1923511&rft.aulast=Royer-Pokora&rft.aufirst=B&rft.au=Loos, U&rft.au=Ludwig, WD&rfr_id=info:sid/en.wikipedia.org:LMO2" class="Z3988">
Boehm T, Spillantini MG, Sofroniew MV, Surani MA, Rabbitts TH (May 1991). "Developmentally regulated and tissue specific expression of mRNAs encoding the two alternative forms of the LIM domain oncogene rhombotin: evidence for thymus expression". Oncogene. 6 (5): 695–703. PMID2052354.695-703&rft.date=1991-05&rft_id=info:pmid/2052354&rft.aulast=Boehm&rft.aufirst=T&rft.au=Spillantini, MG&rft.au=Sofroniew, MV&rft.au=Surani, MA&rft.au=Rabbitts, TH&rfr_id=info:sid/en.wikipedia.org:LMO2" class="Z3988">
Dong WF, Xu Y, Hu QL, Munroe D, Minowada J, Housman DE, Minden MD (November 1995). "Molecular characterization of a chromosome translocation breakpoint t(11;14)(p13;q11) from the cell line KOPT-K1". Leukemia. 9 (11): 1812–1817. PMID7475267.1812-1817&rft.date=1995-11&rft_id=info:pmid/7475267&rft.aulast=Dong&rft.aufirst=WF&rft.au=Xu, Y&rft.au=Hu, QL&rft.au=Munroe, D&rft.au=Minowada, J&rft.au=Housman, DE&rft.au=Minden, MD&rfr_id=info:sid/en.wikipedia.org:LMO2" class="Z3988">
Osada H, Grutz G, Axelson H, Forster A, Rabbitts TH (October 1995). "Association of erythroid transcription factors: complexes involving the LIM protein RBTN2 and the zinc-finger protein GATA1". Proceedings of the National Academy of Sciences of the United States of America. 92 (21): 9585–9589. Bibcode:1995PNAS...92.9585O. doi:10.1073/pnas.92.21.9585. PMC40846. PMID7568177.9585-9589&rft.date=1995-10&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC40846#id-name=PMC&rft_id=info:pmid/7568177&rft_id=info:doi/10.1073/pnas.92.21.9585&rft_id=info:bibcode/1995PNAS...92.9585O&rft.aulast=Osada&rft.aufirst=H&rft.au=Grutz, G&rft.au=Axelson, H&rft.au=Forster, A&rft.au=Rabbitts, TH&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC40846&rfr_id=info:sid/en.wikipedia.org:LMO2" class="Z3988">
Sánchez-García I, Axelson H, Rabbitts TH (April 1995). "Functional diversity of LIM proteins: amino-terminal activation domains in the oncogenic proteins RBTN1 and RBTN2". Oncogene. 10 (7): 1301–1306. PMID7731680.1301-1306&rft.date=1995-04&rft_id=info:pmid/7731680&rft.aulast=Sánchez-García&rft.aufirst=I&rft.au=Axelson, H&rft.au=Rabbitts, TH&rfr_id=info:sid/en.wikipedia.org:LMO2" class="Z3988">
Wadman I, Li J, Bash RO, Forster A, Osada H, Rabbitts TH, Baer R (October 1994). "Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukemia". The EMBO Journal. 13 (20): 4831–4839. doi:10.1002/j.1460-2075.1994.tb06809.x. PMC395422. PMID7957052.4831-4839&rft.date=1994-10&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC395422#id-name=PMC&rft_id=info:pmid/7957052&rft_id=info:doi/10.1002/j.1460-2075.1994.tb06809.x&rft.aulast=Wadman&rft.aufirst=I&rft.au=Li, J&rft.au=Bash, RO&rft.au=Forster, A&rft.au=Osada, H&rft.au=Rabbitts, TH&rft.au=Baer, R&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC395422&rfr_id=info:sid/en.wikipedia.org:LMO2" class="Z3988">
Valge-Archer VE, Osada H, Warren AJ, Forster A, Li J, Baer R, Rabbitts TH (August 1994). "The LIM protein RBTN2 and the basic helix-loop-helix protein TAL1 are present in a complex in erythroid cells". Proceedings of the National Academy of Sciences of the United States of America. 91 (18): 8617–8621. Bibcode:1994PNAS...91.8617V. doi:10.1073/pnas.91.18.8617. PMC44657. PMID8078932.8617-8621&rft.date=1994-08&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC44657#id-name=PMC&rft_id=info:pmid/8078932&rft_id=info:doi/10.1073/pnas.91.18.8617&rft_id=info:bibcode/1994PNAS...91.8617V&rft.aulast=Valge-Archer&rft.aufirst=VE&rft.au=Osada, H&rft.au=Warren, AJ&rft.au=Forster, A&rft.au=Li, J&rft.au=Baer, R&rft.au=Rabbitts, TH&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC44657&rfr_id=info:sid/en.wikipedia.org:LMO2" class="Z3988">
Mao S, Neale GA, Goorha RM (April 1997). "T-cell oncogene rhombotin-2 interacts with retinoblastoma-binding protein 2". Oncogene. 14 (13): 1531–1539. doi:10.1038/sj.onc.1200988. PMID9129143. S2CID25877540.1531-1539&rft.date=1997-04&rft_id=https://api.semanticscholar.org/CorpusID:25877540#id-name=S2CID&rft_id=info:pmid/9129143&rft_id=info:doi/10.1038/sj.onc.1200988&rft.aulast=Mao&rft.aufirst=S&rft.au=Neale, GA&rft.au=Goorha, RM&rfr_id=info:sid/en.wikipedia.org:LMO2" class="Z3988">
Osada H, Grutz GG, Axelson H, Forster A, Rabbitts TH (April 1997). "LIM-only protein Lmo2 forms a protein complex with erythroid transcription factor GATA-1". Leukemia. 11 (Suppl 3): 307–312. PMID9209374.307-312&rft.date=1997-04&rft_id=info:pmid/9209374&rft.aulast=Osada&rft.aufirst=H&rft.au=Grutz, GG&rft.au=Axelson, H&rft.au=Forster, A&rft.au=Rabbitts, TH&rfr_id=info:sid/en.wikipedia.org:LMO2" class="Z3988">
Visvader JE, Mao X, Fujiwara Y, Hahm K, Orkin SH (December 1997). "The LIM-domain binding protein Ldb1 and its partner LMO2 act as negative regulators of erythroid differentiation". Proceedings of the National Academy of Sciences of the United States of America. 94 (25): 13707–13712. Bibcode:1997PNAS...9413707V. doi:10.1073/pnas.94.25.13707. PMC28370. PMID9391090.13707-13712&rft.date=1997-12&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC28370#id-name=PMC&rft_id=info:pmid/9391090&rft_id=info:doi/10.1073/pnas.94.25.13707&rft_id=info:bibcode/1997PNAS...9413707V&rft.aulast=Visvader&rft.aufirst=JE&rft.au=Mao, X&rft.au=Fujiwara, Y&rft.au=Hahm, K&rft.au=Orkin, SH&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC28370&rfr_id=info:sid/en.wikipedia.org:LMO2" class="Z3988">
Kenny DA, Jurata LW, Saga Y, Gill GN (September 1998). "Identification and characterization of LMO4, an LMO gene with a novel pattern of expression during embryogenesis". Proceedings of the National Academy of Sciences of the United States of America. 95 (19): 11257–11262. Bibcode:1998PNAS...9511257K. doi:10.1073/pnas.95.19.11257. PMC21629. PMID9736723.11257-11262&rft.date=1998-09&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC21629#id-name=PMC&rft_id=info:pmid/9736723&rft_id=info:doi/10.1073/pnas.95.19.11257&rft_id=info:bibcode/1998PNAS...9511257K&rft.aulast=Kenny&rft.aufirst=DA&rft.au=Jurata, LW&rft.au=Saga, Y&rft.au=Gill, GN&rft_id=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC21629&rfr_id=info:sid/en.wikipedia.org:LMO2" class="Z3988">