MRTFA: A Critical Protein in Normal and Malignant Hematopoiesis and Beyond

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2021 Mar 16

PMID 33722605

Citations 12

Authors

Fiona Reed

Shannon T Larsuel

Madeline Y Mayday

Vanessa Scanlon

Diane S Krause

Affiliations

Soon will be listed here.

Abstract

Myocardin-related transcription factor A (MRTFA) is a coactivator of serum response factor, a transcription factor that participates in several critical cellular functions including cell growth and apoptosis. MRTFA couples transcriptional regulation to actin cytoskeleton dynamics, and the transcriptional targets of the MRTFA-serum response factor complex include genes encoding cytoskeletal proteins as well as immediate early genes. Previous work has shown that MRTFA promotes the differentiation of many cell types, including various types of muscle cells and hematopoietic cells, and MRTFA's interactions with other protein partners broaden its cellular roles. However, despite being first identified as part of the recurrent t(1;22) chromosomal translocation in acute megakaryoblastic leukemia, the mechanisms by which MRTFA functions in malignant hematopoiesis have yet to be defined. In this review, we provide an in-depth examination of the structure, regulation, and known functions of MRTFA with a focus on hematopoiesis. We conclude by identifying areas of study that merit further investigation.

Citing Articles

Leiomodin 2 neonatal dilated cardiomyopathy mutation results in altered actin gene signatures and cardiomyocyte dysfunction.

Iwanski J, Pappas C, Mayfield R, Farman G, Ahrens-Nicklas R, Churko J NPJ Regen Med. 2024; 9(1):21.

PMID: 39285234 PMC: 11405699. DOI: 10.1038/s41536-024-00366-y.

Ancestral Origins and Admixture History of Kazakhs.

Lei C, Liu J, Zhang R, Pan Y, Lu Y, Gao Y Mol Biol Evol. 2024; 41(7).

PMID: 38995236 PMC: 11272102. DOI: 10.1093/molbev/msae144.

Genomic Variants and Worldwide Epidemiology of Breast Cancer: A Genome-Wide Association Studies Correlation Analysis.

da Costa Nunes G, de Freitas L, Monte N, Albarello Gellen L, Santos A, de Moraes F Genes (Basel). 2024; 15(2).

PMID: 38397135 PMC: 10888129. DOI: 10.3390/genes15020145.

MKL/SRF and Bcl6 mutual transcriptional repression safeguards the fate and positioning of neocortical progenitor cells mediated by RhoA.

Cossard A, Stam K, Smets A, Jossin Y Sci Adv. 2023; 9(46):eadd0676.

PMID: 37967194 PMC: 10651131. DOI: 10.1126/sciadv.add0676.

MRTF-A gain-of-function in mice impairs homeostatic renewal of the intestinal epithelium.

Singh A, Rai A, Weber A, Gericke M, Janssen K, Moser M Cell Death Dis. 2023; 14(9):639.

PMID: 37770456 PMC: 10539384. DOI: 10.1038/s41419-023-06158-4.

References

Sawada T, Nishiyama C, Kishi T, Sasazuki T, Komazawa-Sakon S, Xue X . Fusion of OTT to BSAC results in aberrant up-regulation of transcriptional activity. J Biol Chem. 2008; 283(39):26820-8. PMC: 3258922. DOI: 10.1074/jbc.M802315200. View

Halene S, Gao Y, Hahn K, Massaro S, Italiano Jr J, Schulz V . Serum response factor is an essential transcription factor in megakaryocytic maturation. Blood. 2010; 116(11):1942-50. PMC: 3173990. DOI: 10.1182/blood-2010-01-261743. View

McGee K, Vartiainen M, Khaw P, Treisman R, Bailly M . Nuclear transport of the serum response factor coactivator MRTF-A is downregulated at tensional homeostasis. EMBO Rep. 2011; 12(9):963-70. PMC: 3166461. DOI: 10.1038/embor.2011.141. View

Thakar K, Carroll C . Mkl1-dependent gene activation is sufficient to induce actin cap assembly. Small GTPases. 2017; 10(6):433-440. PMC: 6748361. DOI: 10.1080/21541248.2017.1328303. View

Scharenberg M, Chiquet-Ehrismann R, Asparuhova M . Megakaryoblastic leukemia protein-1 (MKL1): Increasing evidence for an involvement in cancer progression and metastasis. Int J Biochem Cell Biol. 2010; 42(12):1911-4. DOI: 10.1016/j.biocel.2010.08.014. View

Muehlich S, Wang R, Lee S, Lewis T, Dai C, Prywes R . Serum-induced phosphorylation of the serum response factor coactivator MKL1 by the extracellular signal-regulated kinase 1/2 pathway inhibits its nuclear localization. Mol Cell Biol. 2008; 28(20):6302-13. PMC: 2577419. DOI: 10.1128/MCB.00427-08. View

Li J, Zhu X, Chen M, Cheng L, Zhou D, Lu M . Myocardin-related transcription factor B is required in cardiac neural crest for smooth muscle differentiation and cardiovascular development. Proc Natl Acad Sci U S A. 2005; 102(25):8916-21. PMC: 1157054. DOI: 10.1073/pnas.0503741102. View

Stern S, Debre E, Stritt C, Berger J, Posern G, Knoll B . A nuclear actin function regulates neuronal motility by serum response factor-dependent gene transcription. J Neurosci. 2009; 29(14):4512-8. PMC: 6665722. DOI: 10.1523/JNEUROSCI.0333-09.2009. View

Smith E, Thon J, Devine M, Lin S, Schulz V, Guo Y . MKL1 and MKL2 play redundant and crucial roles in megakaryocyte maturation and platelet formation. Blood. 2012; 120(11):2317-29. PMC: 3447785. DOI: 10.1182/blood-2012-04-420828. View

10.

Tijssen M, Ghevaert C . Transcription factors in late megakaryopoiesis and related platelet disorders. J Thromb Haemost. 2013; 11(4):593-604. PMC: 3824237. DOI: 10.1111/jth.12131. View

11.

Branehog I, Ridell B, Swolin B, WEINFELD A . Megakaryocyte quantifications in relation to thrombokinetics in primary thrombocythaemia and allied diseases. Scand J Haematol. 1975; 15(5):321-32. DOI: 10.1111/j.1600-0609.1975.tb01087.x. View

12.

Laurent A, Kotecha R, Malinge S . Gain of chromosome 21 in hematological malignancies: lessons from studying leukemia in children with Down syndrome. Leukemia. 2020; 34(8):1984-1999. PMC: 7387246. DOI: 10.1038/s41375-020-0854-5. View

13.

Asparuhova M, Secondini C, Ruegg C, Chiquet-Ehrismann R . Mechanism of irradiation-induced mammary cancer metastasis: A role for SAP-dependent Mkl1 signaling. Mol Oncol. 2015; 9(8):1510-27. PMC: 5528797. DOI: 10.1016/j.molonc.2015.04.003. View

14.

Cen B, Selvaraj A, Burgess R, Hitzler J, Ma Z, Morris S . Megakaryoblastic leukemia 1, a potent transcriptional coactivator for serum response factor (SRF), is required for serum induction of SRF target genes. Mol Cell Biol. 2003; 23(18):6597-608. PMC: 193697. DOI: 10.1128/MCB.23.18.6597-6608.2003. View

15.

Cheng E, Luo Q, Bruscia E, Renda M, Troy J, Massaro S . Role for MKL1 in megakaryocytic maturation. Blood. 2009; 113(12):2826-34. PMC: 2661865. DOI: 10.1182/blood-2008-09-180596. View

16.

Oh J, Richardson J, Olson E . Requirement of myocardin-related transcription factor-B for remodeling of branchial arch arteries and smooth muscle differentiation. Proc Natl Acad Sci U S A. 2005; 102(42):15122-7. PMC: 1257726. DOI: 10.1073/pnas.0507346102. View

17.

Gruber T, Downing J . The biology of pediatric acute megakaryoblastic leukemia. Blood. 2015; 126(8):943-9. PMC: 4551356. DOI: 10.1182/blood-2015-05-567859. View

18.

MacKinnon R, Wall M, Zordan A, Nutalapati S, Mercer B, Peverall J . Genome organization and the role of centromeres in evolution of the erythroleukaemia cell line HEL. Evol Med Public Health. 2014; 2013(1):225-40. PMC: 3868402. DOI: 10.1093/emph/eot020. View

19.

Xu W, Zhao Q, Wu M, Fang M, Xu Y . MKL1 mediates TNF-α induced pro-inflammatory transcription by bridging the crosstalk between BRG1 and WDR5. J Biomed Res. 2017; 33(3):164-172. PMC: 6551423. DOI: 10.7555/JBR.32.20170025. View

20.

Aravind L, Koonin E . SAP - a putative DNA-binding motif involved in chromosomal organization. Trends Biochem Sci. 2000; 25(3):112-4. DOI: 10.1016/s0968-0004(99)01537-6. View