MKL1 explained

MKL/megakaryoblastic leukemia 1 (also termed MRTFA/myocardin related transcription factor A) is a protein that in humans is encoded by the MKL1 gene.^{[1] [2] [3] [4]}

Function

The protein encoded by this gene is regulated by the actin cytoskeleton and is shuttled between the cytoplasm and the nucleus as a result of actin dynamics.^[5] In the nucleus, it coactivates the transcription factor serum response factor,^[6] a key regulator of smooth muscle cell differentiation, in an interaction mediated by its Basic domain. It is closely related to MKL2 and myocardin, with which it shares five key conserved structural domains.^[7]

Clinical significance

This gene is involved in a specific translocation event that creates a fusion of this gene and the RNA-binding motif protein-15 gene. This translocation has been associated with acute megakaryocytic leukemia.^[4] It also functions in the process of normal megakaryocyte maturation.^[8]

Research

Evalarted MKL1 expression is observed in breast cancer and can predict chemosensitivity and patient survival. MKL1 may be a promising biomarker of clinical value for breast cancer.^[9]

See also

• Serum response factor

Further reading

• Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T . Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones . DNA Research . 9 . 3 . 99–106 . June 2002 . 12168954 . 10.1093/dnares/9.3.99 . free .
• Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP . 6 . The DNA sequence of human chromosome 22 . Nature . 402 . 6761 . 489–495 . December 1999 . 10591208 . 10.1038/990031 . free . 1999Natur.402..489D .
• Nagase T, Kikuno R, Ishikawa KI, Hirosawa M, Ohara O . Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro . DNA Research . 7 . 1 . 65–73 . February 2000 . 10718198 . 10.1093/dnares/7.1.65 . free .
• Mercher T, Coniat MB, Monni R, Mauchauffe M, Nguyen Khac F, Gressin L, Mugneret F, Leblanc T, Dastugue N, Berger R, Bernard OA . 6 . Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia . Proceedings of the National Academy of Sciences of the United States of America . 98 . 10 . 5776–5779 . May 2001 . 11344311 . 33289 . 10.1073/pnas.101001498 . free . 2001PNAS...98.5776M .
• Wang D, Chang PS, Wang Z, Sutherland L, Richardson JA, Small E, Krieg PA, Olson EN . 6 . Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor . Cell . 105 . 7 . 851–862 . June 2001 . 11439182 . 10.1016/S0092-8674(01)00404-4 . free .
• Wang DZ, Li S, Hockemeyer D, Sutherland L, Wang Z, Schratt G, Richardson JA, Nordheim A, Olson EN . 6 . Potentiation of serum response factor activity by a family of myocardin-related transcription factors . Proceedings of the National Academy of Sciences of the United States of America . 99 . 23 . 14855–14860 . November 2002 . 12397177 . 137508 . 10.1073/pnas.222561499 . free . 2002PNAS...9914855W .
• Cen B, Selvaraj A, Burgess RC, Hitzler JK, Ma Z, Morris SW, Prywes R . Megakaryoblastic leukemia 1, a potent transcriptional coactivator for serum response factor (SRF), is required for serum induction of SRF target genes . Molecular and Cellular Biology . 23 . 18 . 6597–6608 . September 2003 . 12944485 . 193697 . 10.1128/MCB.23.18.6597-6608.2003 .
• Selvaraj A, Prywes R . Megakaryoblastic leukemia-1/2, a transcriptional co-activator of serum response factor, is required for skeletal myogenic differentiation . The Journal of Biological Chemistry . 278 . 43 . 41977–41987 . October 2003 . 14565952 . 10.1074/jbc.M305679200 . free .
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP . 6 . Large-scale characterization of HeLa cell nuclear phosphoproteins . Proceedings of the National Academy of Sciences of the United States of America . 101 . 33 . 12130–12135 . August 2004 . 15302935 . 514446 . 10.1073/pnas.0404720101 . free . 2004PNAS..10112130B .
• Selvaraj A, Prywes R . Expression profiling of serum inducible genes identifies a subset of SRF target genes that are MKL dependent . BMC Molecular Biology . 5 . 13 . August 2004 . 15329155 . 516031 . 10.1186/1471-2199-5-13 . free .
• Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I . 6 . A genome annotation-driven approach to cloning the human ORFeome . Genome Biology . 5 . 10 . R84 . 2005 . 15461802 . 545604 . 10.1186/gb-2004-5-10-r84 . free .
• Hsiao HH, Yang MY, Liu YC, Hsiao HP, Tseng SB, Chao MC, Liu TC, Lin SF . 6 . RBM15-MKL1 (OTT-MAL) fusion transcript in an adult acute myeloid leukemia patient . American Journal of Hematology . 79 . 1 . 43–45 . May 2005 . 15849773 . 10.1002/ajh.20298 . 30859557 . free .
• Nakagawa K, Kuzumaki N . Transcriptional activity of megakaryoblastic leukemia 1 (MKL1) is repressed by SUMO modification . Genes to Cells . 10 . 8 . 835–850 . August 2005 . 16098147 . 10.1111/j.1365-2443.2005.00880.x . free .

Notes and References

1. Ma Z, Morris SW, Valentine V, Li M, Herbrick JA, Cui X, Bouman D, Li Y, Mehta PK, Nizetic D, Kaneko Y, Chan GC, Chan LC, Squire J, Scherer SW, Hitzler JK . 6 . Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia . Nature Genetics . 28 . 3 . 220–221 . July 2001 . 11431691 . 10.1038/90054 . 36236342 .
2. Sasazuki T, Sawada T, Sakon S, Kitamura T, Kishi T, Okazaki T, Katano M, Tanaka M, Watanabe M, Yagita H, Okumura K, Nakano H . 6 . Identification of a novel transcriptional activator, BSAC, by a functional cloning to inhibit tumor necrosis factor-induced cell death . The Journal of Biological Chemistry . 277 . 32 . 28853–28860 . August 2002 . 12019265 . 10.1074/jbc.M203190200 . free .
3. Du KL, Chen M, Li J, Lepore JJ, Mericko P, Parmacek MS . Megakaryoblastic leukemia factor-1 transduces cytoskeletal signals and induces smooth muscle cell differentiation from undifferentiated embryonic stem cells . The Journal of Biological Chemistry . 279 . 17 . 17578–17586 . April 2004 . 14970199 . 10.1074/jbc.M400961200 . free .
4. Web site: Entrez Gene: MKL1 megakaryoblastic leukemia (translocation) 1.
5. Vartiainen MK, Guettler S, Larijani B, Treisman R . Nuclear actin regulates dynamic subcellular localization and activity of the SRF cofactor MAL . Science . 316 . 5832 . 1749–1752 . June 2007 . 17588931 . 10.1126/science.1141084 . 44910416 . 2007Sci...316.1749V .
6. Miralles F, Posern G, Zaromytidou AI, Treisman R . Actin dynamics control SRF activity by regulation of its coactivator MAL . Cell . 113 . 3 . 329–342 . May 2003 . 12732141 . 10.1016/S0092-8674(03)00278-2 . free .
7. Wang DZ, Li S, Hockemeyer D, Sutherland L, Wang Z, Schratt G, Richardson JA, Nordheim A, Olson EN . 6 . Potentiation of serum response factor activity by a family of myocardin-related transcription factors . Proceedings of the National Academy of Sciences of the United States of America . 99 . 23 . 14855–14860 . November 2002 . 12397177 . 137508 . 10.1073/pnas.222561499 . free . 2002PNAS...9914855W .
8. Cheng EC, Luo Q, Bruscia EM, Renda MJ, Troy JA, Massaro SA, Tuck D, Schulz V, Mane SM, Berliner N, Sun Y, Morris SW, Qiu C, Krause DS . 6 . Role for MKL1 in megakaryocytic maturation . Blood . 113 . 12 . 2826–2834 . March 2009 . 19136660 . 2661865 . 10.1182/blood-2008-09-180596 .
9. Hua Y, Yang M . The prognostic value of MKL1 in predicting breast cancer immune infiltrates and chemosensitivity . Bosnian Journal of Basic Medical Sciences . 22 . 3 . 382–394 . June 2022 . 34761735 . 9162751 . 10.17305/bjbms.2021.6306 .