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Gene Review

MKL1  -  megakaryoblastic leukemia (translocation) 1

Homo sapiens

Synonyms: BSAC, KIAA1438, MAL, MKL/myocardin-like protein 1, MRTF-A, ...
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Disease relevance of MKL1


Psychiatry related information on MKL1

  • Outcome measures included the Motor Activity Log for very low functioning patients (Grade 5 MAL), upper extremity portion of the Fugl-Meyer Motor Assessment, Graded Wolf Motor Function Test - for very low functioning patients (gWMFT- Grade 5), and Modified Ashworth Scale [7].

High impact information on MKL1


Chemical compound and disease context of MKL1


Biological context of MKL1


Anatomical context of MKL1

  • In NIH3T3 fibroblasts MKL1 localizes to the cytoplasm and translocates to the nucleus in response to serum stimulation, actin treadmilling, and RhoA signaling [21].
  • Together, these data were consistent with a model wherein MKL1 transduces signals from the cytoskeleton to the nucleus in SMCs and regulates SRF-dependent SMC differentiation autonomously or in concert with myocardin [21].
  • RBM15 and MKL1 mutational screening in megakaryoblastic leukemia cell lines and clinical samples [24].
  • MKL1 expression was found in newborn rat cortical or hippocampal neurons in culture as well as in adult rat forebrain [25].
  • Immunostaining demonstrated constitutive nuclear localization of MKL1 in the CA1 region of the hippocampus, in the deep layers of the neocortex, and in cultured neurons [25].

Associations of MKL1 with chemical compounds


Regulatory relationships of MKL1


Other interactions of MKL1

  • It has been shown that MKL1 functions as a RhoA-regulated transcriptional coactivator of serum response factor (SRF) [22].
  • Forced expression of a dominant-negative MKL1 mutant reduces myocardin-induced activation of the SMC-specific SM22alpha promoter [21].
  • In contrast, in SMCs MKL1 is observed exclusively in the nucleus regardless of serum conditions or RhoA signaling [21].
  • Parathyroid hormone-related protein, chromogranin A, and calcitonin gene products in the neuroendocrine skin carcinoma cell lines MKL1 and MKL2 [34].
  • These results suggest that neuronal MKL1 contributes to SRF-regulated gene expression induced by BDNF or synaptic activity [25].

Analytical, diagnostic and therapeutic context of MKL1


  1. A novel real-time RT-PCR assay for quantification of OTT-MAL fusion transcript reliable for diagnosis of t(1;22) and minimal residual disease (MRD) detection. Ballerini, P., Blaise, A., Mercher, T., Pellegrino, B., Perot, C., van den Akker, J., Gatbois, E., Adam, M., Douay, L., Berger, R., Bernard, O., Landman-Parker, J. Leukemia (2003) [Pubmed]
  2. Acute megakaryoblastic leukaemia: a national clinical and biological study of 53 adult and childhood cases by the Groupe Français d'Hématologie Cellulaire (GFHC). Duchayne, E., Fenneteau, O., Pages, M.P., Sainty, D., Arnoulet, C., Dastugue, N., Garand, R., Flandrin, G. Leuk. Lymphoma (2003) [Pubmed]
  3. Hematologic neoplasia associated with primary mediastinal germ-cell tumors. Nichols, C.R., Roth, B.J., Heerema, N., Griep, J., Tricot, G. N. Engl. J. Med. (1990) [Pubmed]
  4. Exposure by desialylation of myeloid antigens on acute lymphoblastic leukemia cells. Stockinger, H., Majdic, O., Liszka, K., Aberer, W., Bettelheim, P., Lutz, D., Knapp, W. J. Natl. Cancer Inst. (1984) [Pubmed]
  5. Cytogenetic and molecular studies of Down syndrome individuals with leukemia. Shen, J.J., Williams, B.J., Zipursky, A., Doyle, J., Sherman, S.L., Jacobs, P.A., Shugar, A.L., Soukup, S.W., Hassold, T.J. Am. J. Hum. Genet. (1995) [Pubmed]
  6. Fusion of OTT to BSAC results in aberrant up-regulation of transcriptional activity. Sawada, T., Nishiyama, C., Kishi, T., Sasazuki, T., Komazawa-Sakon, S., Xue, X., Piao, J.H., Ogata, H., Nakayama, J., Taki, T., Hayashi, Y., Watanabe, M., Yagita, H., Okumura, K., Nakano, H. J. Biol. Chem. (2008) [Pubmed]
  7. A treatment for a chronic stroke patient with a plegic hand combining CI therapy with conventional rehabilitation procedures: Case report. Taub, E., Uswatt, G., Bowman, M.H., Taub, E., Uswatte, G., Delgado, A., Bryson, C., Morris, D.M., McKay, S., Mark, V.W. NeuroRehabilitation. (2006) [Pubmed]
  8. An inherited mutation leading to production of only the short isoform of GATA-1 is associated with impaired erythropoiesis. Hollanda, L.M., Lima, C.S., Cunha, A.F., Albuquerque, D.M., Vassallo, J., Ozelo, M.C., Joazeiro, P.P., Saad, S.T., Costa, F.F. Nat. Genet. (2006) [Pubmed]
  9. Acquired mutations in GATA1 in the megakaryoblastic leukemia of Down syndrome. Wechsler, J., Greene, M., McDevitt, M.A., Anastasi, J., Karp, J.E., Le Beau, M.M., Crispino, J.D. Nat. Genet. (2002) [Pubmed]
  10. Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia. Ma, Z., Morris, S.W., Valentine, V., Li, M., Herbrick, J.A., Cui, X., Bouman, D., Li, Y., Mehta, P.K., Nizetic, D., Kaneko, Y., Chan, G.C., Chan, L.C., Squire, J., Scherer, S.W., Hitzler, J.K. Nat. Genet. (2001) [Pubmed]
  11. A nuclear MAL-function links Rho to SRF. Settleman, J. Mol. Cell (2003) [Pubmed]
  12. Mediastinal germ cell tumor and acute megakaryoblastic leukemia. Domingo, A., Romagosa, V., Callis, M., Vivancos, P., Guionnet, N., Soler, J. Ann. Intern. Med. (1989) [Pubmed]
  13. SCAI acts as a suppressor of cancer cell invasion through the transcriptional control of beta1-integrin. Brandt, D.T., Baarlink, C., Kitzing, T.M., Kremmer, E., Ivaska, J., Nollau, P., Grosse, R. Nat. Cell. Biol. (2009) [Pubmed]
  14. Myocardin-related transcription factors and SRF are required for cytoskeletal dynamics and experimental metastasis. Medjkane, S., Perez-Sanchez, C., Gaggioli, C., Sahai, E., Treisman, R. Nat. Cell. Biol. (2009) [Pubmed]
  15. A mutation in the translation initiation codon of Gata-1 disrupts megakaryocyte maturation and causes thrombocytopenia. Majewski, I.J., Metcalf, D., Mielke, L.A., Krebs, D.L., Ellis, S., Carpinelli, M.R., Mifsud, S., Di Rago, L., Corbin, J., Nicola, N.A., Hilton, D.J., Alexander, W.S. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  16. Differentiation patterns in the blastic phase of chronic myeloid leukemia. Griffin, J.D., Todd, R.F., Ritz, J., Nadler, L.M., Canellos, G.P., Rosenthal, D., Gallivan, M., Beveridge, R.P., Weinstein, H., Karp, D., Schlossman, S.F. Blood (1983) [Pubmed]
  17. dl-alpha-tocopherol, a potent inhibitor of phorbol ester induced shape change of erythro- and megakaryoblastic leukemia cells. Steiner, M., Li, W., Ciaramella, J.M., Anagnostou, A., Sigounas, G. J. Cell. Physiol. (1997) [Pubmed]
  18. Myeloperoxidase-positive acute megakaryoblastic leukemia. Moscinski, L.C., So, A.L., Russell, J.E., Kant, J.A., Prystowsky, M.B. Am. J. Clin. Pathol. (1989) [Pubmed]
  19. Evaluation of a 10 {micro}g cefoxitin disc for the detection of methicillin resistance in Staphylococcus aureus by BSAC methodology. Andrews, J., Brenwald, N., Brown, D.F., Perry, J., King, A., Gemmell, C. J. Antimicrob. Chemother. (2005) [Pubmed]
  20. Megakaryoblastic leukemia 1, a potent transcriptional coactivator for serum response factor (SRF), is required for serum induction of SRF target genes. Cen, B., Selvaraj, A., Burgess, R.C., Hitzler, J.K., Ma, Z., Morris, S.W., Prywes, R. Mol. Cell. Biol. (2003) [Pubmed]
  21. Megakaryoblastic leukemia factor-1 transduces cytoskeletal signals and induces smooth muscle cell differentiation from undifferentiated embryonic stem cells. Du, K.L., Chen, M., Li, J., Lepore, J.J., Mericko, P., Parmacek, M.S. J. Biol. Chem. (2004) [Pubmed]
  22. Transcriptional activity of megakaryoblastic leukemia 1 (MKL1) is repressed by SUMO modification. Nakagawa, K., Kuzumaki, N. Genes Cells (2005) [Pubmed]
  23. Myocardin/MKL family of SRF coactivators: key regulators of immediate early and muscle specific gene expression. Cen, B., Selvaraj, A., Prywes, R. J. Cell. Biochem. (2004) [Pubmed]
  24. RBM15 and MKL1 mutational screening in megakaryoblastic leukemia cell lines and clinical samples. Kawaguchi, H., Hitzler, J.K., Ma, Z., Morris, S.W. Leukemia (2005) [Pubmed]
  25. Role of megakaryoblastic acute leukemia-1 in ERK1/2-dependent stimulation of serum response factor-driven transcription by BDNF or increased synaptic activity. Kalita, K., Kharebava, G., Zheng, J.J., Hetman, M. J. Neurosci. (2006) [Pubmed]
  26. Immunophenotyping of acute myeloid leukemia using monoclonal antibodies and the alkaline phosphatase-antialkaline phosphatase technique. Hanson, C.A., Gajl-Peczalska, K.J., Parkin, J.L., Brunning, R.D. Blood (1987) [Pubmed]
  27. Tentative minimum inhibitory concentration and zone diameter breakpoints for moxifloxacin using BSAC criteria. Andrews, J.M., Ashby, J.P., Jevons, G.M., Wise, R. J. Antimicrob. Chemother. (1999) [Pubmed]
  28. Reply to: Ciprofloxacin susceptibility testing of enterococcal urinary isolates in accordance with BSAC guidelines. Andrews, J.M., Wise, R. J. Antimicrob. Chemother. (2002) [Pubmed]
  29. Comparison of three standardized disc susceptibility testing methods for colistin. Tan, T.Y., Ng, L.S. J. Antimicrob. Chemother. (2006) [Pubmed]
  30. Identification of a novel transcriptional activator, BSAC, by a functional cloning to inhibit tumor necrosis factor-induced cell death. Sasazuki, T., Sawada, T., Sakon, S., Kitamura, T., Kishi, T., Okazaki, T., Katano, M., Tanaka, M., Watanabe, M., Yagita, H., Okumura, K., Nakano, H. J. Biol. Chem. (2002) [Pubmed]
  31. Acute panmyelosis with myelofibrosis: an entity distinct from acute megakaryoblastic leukemia. Orazi, A., O'Malley, D.P., Jiang, J., Vance, G.H., Thomas, J., Czader, M., Fang, W., An, C., Banks, P.M. Mod. Pathol. (2005) [Pubmed]
  32. Enhanced expression of thrombomodulin by intracellular cyclic AMP-increasing agents in two human megakaryoblastic leukemia cell lines. Ito, T., Ogura, M., Morishita, Y., Takamatsu, J., Maruyama, I., Yamamoto, S., Ogawa, K., Saito, H. Thromb. Res. (1990) [Pubmed]
  33. Detection of platelet-specific protein mRNAs in different megakaryoblasts using the reverse transcriptase polymerase chain reaction. Yasunaga, M., Ryo, R., Sugano, W., Yamaguchi, N. Leuk. Lymphoma (1992) [Pubmed]
  34. Parathyroid hormone-related protein, chromogranin A, and calcitonin gene products in the neuroendocrine skin carcinoma cell lines MKL1 and MKL2. Martin, E.M., Gould, V.E., Hoog, A., Rosen, S.T., Radosevich, J.A., Deftos, L.J. Bone and mineral. (1991) [Pubmed]
  35. JAK2T875N is a novel activating mutation that results in myeloproliferative disease with features of megakaryoblastic leukemia in a murine bone marrow transplantation model. Mercher, T., Wernig, G., Moore, S.A., Levine, R.L., Gu, T.L., Fr??hling, S., Cullen, D., Polakiewicz, R.D., Bernard, O.A., Boggon, T.J., Lee, B.H., Gilliland, D.G. Blood (2006) [Pubmed]
  36. Uncoordinated expression of fibrinogen compared with thrombospondin and von Willebrand factor in maturing human megakaryocytes. Cramer, E.M., Debili, N., Martin, J.F., Gladwin, A.M., Breton-Gorius, J., Harrison, P., Savidge, G.F., Vainchenker, W. Blood (1989) [Pubmed]
  37. Aclacinomycin A and etoposide (VP-16-213): an effective regimen in previously treated patients with refractory acute myelogenous leukemia. Rowe, J.M., Chang, A.Y., Bennett, J.M. Blood (1988) [Pubmed]
  38. Diagnosis of acute megakaryoblastic leukemia by flow cytometry and immunoalkaline phosphatase techniques. Utilization of new monoclonal antibodies. Choate, J.J., Domenico, D.R., McGraw, T.P., Fareed, J., Molnar, Z., Schumacher, H.R. Am. J. Clin. Pathol. (1988) [Pubmed]
  39. Comments on the report of the BSAC working party (WP) on self-medication of antibacterials without prescription. Alfandari, S., Beaucaire, G. J. Antimicrob. Chemother. (2000) [Pubmed]
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