To stay in shape and keep moving: MLL emerges as a new transcriptional regulator of Rho GTPases

References

• Mosaddeghzadeh N, Ahmadian MR. ’the rho family gtpases: mechanisms of regulation and signaling’. Cells. 2021 Jul 01;10(7):1831. MDPI. doi: 10.3390/cells10071831
   PubMed Web of Science ®Google Scholar
• Mosaddeghzadeh N, Kazemein Jasemi NS, Majolée J, et al. Electrostatic forces mediate the specificity of RHO GTPase-GDI interactions. Int J Mol Sci. 2021 Nov;22(22):12493. doi: 10.3390/ijms222212493
   PubMed Web of Science ®Google Scholar
• Chinchole A, Lone KA, Tyagi S. MLL regulates the actin cytoskeleton and cell migration by stabilising Rho GTPases via the expression of RhoGDI1. J Cell Sci. 2022 Oct;135(20): doi: 10.1242/JCS.260042
   PubMed Web of Science ®Google Scholar
• Small JV, Rottner K, Hahne P, et al. Visualising the actin cytoskeleton. Microsc Res Tech. 1999;47(1):3–17. doi:10.1002/(SICI)1097-0029(19991001)47:1<3:AID-JEMT2>3.0.CO;2-2
   PubMed Web of Science ®Google Scholar
• Ridley AJ, Hall A. The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell. 1992;70(3):389–399. doi: 10.1016/0092-8674(92)90163-7
   PubMed Web of Science ®Google Scholar
• Ridley AJ, Paterson HF, Johnston CL, et al. The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell. 1992;70(3):401–410. doi: 10.1016/0092-8674(92)90164-8
   PubMed Web of Science ®Google Scholar
• Nobes CD, Hall A. Rho, rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell. 1995;81(1):53–62. doi: 10.1016/0092-8674(95)90370-4
   PubMed Web of Science ®Google Scholar
• Tojkander S, Gateva G, Lappalainen P. Actin stress fibers – assembly, dynamics and biological roles. 2012. doi: 10.1242/jcs.098087
   Google Scholar
• Pascual-Vargas P, Cooper S, Sero J, et al. RNAi screens for Rho GTPase regulators of cell shape and YAP/TAZ localisation in triple negative breast cancer. Sci Data. 2017;4(1):1–13. doi: 10.1038/sdata.2017.18
   Google Scholar
• Dimchev V, Lahmann I, Koestler SA, et al. Induced Arp2/3 complex depletion increases FMNL2/3 formin expression and filopodia formation. Front Cell Dev Biol. 2021;9:634708. DOI:10.3389/fcell.2021.634708
   PubMed Web of Science ®Google Scholar
• Artinger EL, Mishra BP, Zaffuto KM, et al. An MLL-dependent network sustains hematopoiesis. Proc Natl Acad Sci U S A. 2013;110(29):12000–12005. doi: 10.1073/pnas.1301278110
   PubMed Web of Science ®Google Scholar
• Malik KK, Sridhara SC, Lone KA, et al. MLL methyltransferases regulate H3K4 methylation to ensure CENP-A assembly at human centromeres. PLoS Biol. 2023 Jun;21(6):e3002161. doi: 10.1371/journal.pbio.3002161
   PubMed Web of Science ®Google Scholar
• Dahéron L, Veinstein A, Brizard F, et al. Human LPP gene is fused to MLL in a secondary acute leukemia with a t(3;11) (q28;q23). Genes Chromosomes Cancer. 2001;31(4):382–389. doi: 10.1002/gcc.1157
   PubMed Web of Science ®Google Scholar
• Eguchi M, Eguchi-Ishimae M, Seto M, et al. GPHN, a novel partner gene fused to MLL in a leukemia with t(11;14)(q23;q24). Genes Chromosomes Cancer. 2001;321:212–221. doi: 10.1002/gcc.1185
   PubMedGoogle Scholar
• Duhoux FP, Ameye G, Libouton J-M, et al. The t(11;19(q23;p13) fusing MLL with MYO1F is recurrent in infant acute myeloid leukemias. Leuk Res. 2011;35(9):e171–e172. doi: 10.1016/j.leukres.2011.04.022
   PubMed Web of Science ®Google Scholar
• Manara E, Baron E, Tregnago C, et al. MLL-AF6 fusion oncogene sequesters AF6 into the nucleus to trigger RAS activation in myeloid leukemia. Blood. 2014;124(2):263–272. doi: 10.1182/blood-2013-09-525741
   PubMed Web of Science ®Google Scholar
• Von Bergh ARM, Wijers PM, Groot AJ, et al. Identification of a novel RAS GTPpase-activating protein (RASGAP) gene at 9q34 as an MLL fusion partner in a patient with De Novo acute leukemia. Genes Chromosomes Cancer. 2004 Apr;39(4):324–334. doi: 10.1002/gcc.20004
   PubMed Web of Science ®Google Scholar
• Cóser VM, Meyer C, Basegio R, et al. Nebulette is the second member of the nebulin family fused to the MLL gene in infant leukemia. Cancer Genet Cytogenet. 2010 Apr;198(2):151–154. doi: 10.1016/j.cancergencyto.2009.12.013
   PubMedGoogle Scholar
• Marschalek R. ‘Classification of mixed-lineage leukemia fusion partners predicts additional cancer pathways’. Ann Lab Med. 2016 Mar 01;36(2):85–100. Seoul National University. doi: 10.3343/alm.2016.36.2.85
   PubMed Web of Science ®Google Scholar
• Meyer C, Burmeister T, Gröger D, et al. The MLL recombinome of acute leukemias in 2017. Leukemia. 2018 Feb;32(2):273–284. doi: 10.1038/leu.2017.213
   PubMed Web of Science ®Google Scholar
• Burridge K, Guilluy C. Focal adhesions, stress fibers and mechanical tension. Exp Cell Res. 2016;343(1):14–20. doi: 10.1016/j.yexcr.2015.10.029
   PubMed Web of Science ®Google Scholar
• Garcia-Mata R, Boulter E, Burridge K. The “invisible hand”: regulation of RHO GTPases by RHOGDIs. Nat Rev Mol Cell Biol. 2011;12(8):493–504. doi:10.1038/nrm3153
   PubMed Web of Science ®Google Scholar
• Boulter E, Garcia-Mata R, Guilluy C, et al. Regulation of Rho GTPase crosstalk, degradation and activity by RhoGDI1. Nat Cell Biol. 2010;12(5):477–483. doi: 10.1038/ncb2049
   PubMed Web of Science ®Google Scholar
• Wang P, Lin C, Smith ER, et al. Global analysis of H3K4 methylation defines MLL family member targets and points to a role for MLL1-Mediated H3K4 methylation in the regulation of transcriptional initiation by RNA polymerase II. Mol Cell Biol. 2009 Nov;29(22):6074–6085. doi: 10.1128/mcb.00924-09
   PubMed Web of Science ®Google Scholar
• Zhang Y, Ji T, Ma S, et al. RETRACTED: MLL1 promotes migration and invasion of fibroblast-like synoviocytes in rheumatoid arthritis by activating the TRIF/NF-κB signaling pathway via H3K4me3 enrichment in the TLR4 promoter region. Int Immunopharmacol. 2020;82(71):106220. doi:10.1016/j.intimp.2020.106220
   PubMedGoogle Scholar
• Malek R, Gajula RP, Williams RD, et al. TWIST1-WDR5-hottip regulates Hoxa9 chromatin to facilitate prostate cancer metastasis. Cancer Res. 2017;77(12):3181–3193. doi: 10.1158/0008-5472.CAN-16-2797
   PubMed Web of Science ®Google Scholar
• He FX, Zhang LL, Jin PF, et al. DPY30 regulates cervical squamous cell carcinoma by mediating epithelial-mesenchymal transition (EMT). Onco Targets Ther. 2019;12:7139–7147. doi:10.2147/OTT.S209315
   PubMed Web of Science ®Google Scholar
• Wang P, Dreger M, Madrazo E, et al. WDR5 modulates cell motility and morphology and controls nuclear changes induced by a 3D environment. Proc Natl Acad Sci U S A. 2018;115(34):8581–8586. doi: 10.1073/pnas.1719405115
   PubMed Web of Science ®Google Scholar
• Issaeva I, Zonis Y, Rozovskaia T, et al. Knockdown of ALR (MLL2) reveals ALR target genes and leads to alterations in cell adhesion and growth. Mol Cell Biol. 2007;27(5):1889–1903. doi: 10.1128/mcb.01506-06
   PubMed Web of Science ®Google Scholar
• Xia M, Xu L, Leng Y, et al. Downregulation of MLL3 in esophageal squamous cell carcinoma is required for the growth and metastasis of cancer cells. pp. 605–613. 2015. doi: 10.1007/s13277-014-2616-3
   Google Scholar
• Blanchoin L, Boujemaa-Paterski R, Sykes C, et al. Actin dynamics, architecture, and mechanics in cell motility. Physiol Rev. 2014;94(1):235–263. doi: 10.1152/physrev.00018.2013
   PubMed Web of Science ®Google Scholar
• Azim AC, Barkalow K, Chou J, et al. Activation of the small GTPases, rac and cdc42, after ligation of the platelet PAR-1 receptor. Blood. 2000 Feb;95(3):959–964. doi: 10.1182/blood.V95.3.959.003k22_959_964
   PubMed Web of Science ®Google Scholar
• van Nieuw Amerongen GP, van Delft S, Vermeer MA, et al. Activation of RhoA by thrombin in endothelial hyperpermeability: role of Rho kinase and protein tyrosine kinases. Circ Res. 2000 Aug;87(4):335–340. doi: 10.1161/01.res.87.4.335
   PubMed Web of Science ®Google Scholar
• Yu J, Zhang D, Liu J, et al. RhoGDI SUMOylation at Lys-138 increases its binding activity to Rho GTPase and its inhibiting cancer cell motility. J Biol Chem. 2012;287(17):13752–13760. doi: 10.1074/jbc.M111.337469
   PubMed Web of Science ®Google Scholar
• Mohan M, Lin C, Guest E, et al. Licensed to elongate: a molecular mechanism for MLL-based leukaemogenesis. Nat Rev Cancer. 2010;10(10):721–728. doi: 10.1038/nrc2915
   PubMed Web of Science ®Google Scholar
• Walf-Vorderwülbecke V, de Boer J, Horton SJ, et al. Frat2 mediates the oncogenic activation of rac by MLL fusions. Blood. 2012 Dec;120(24):4819–4828. doi: 10.1182/blood-2012-05-432534
   PubMed Web of Science ®Google Scholar
• Borkhardt A, Bojesen S, Haas OA, et al. The human GRAF gene is fused to MLL in a unique t(5;11)(q31;q23) and both alleles are disrupted in three cases of myelodysplastic syndrome/acute myeloid leukemia with a deletion 5q. Proc Nat Acad Sci. 2000;97(16):9168–9173. [Online]. Available: www.pnas.org
   PubMed Web of Science ®Google Scholar
• Kourlas PJ, Strout, MP, Becknell, B, et al. Identification of a gene at 11q23 encoding a guanine nucleotide exchange factor: evidence for its fusion with MLL in acute myeloid leukemia. Proc Natl Acad Sci USA. 2000;97(5):2145–2150. doi: 10.1073/pnas.040569197
   PubMed Web of Science ®Google Scholar
• Yoshida A, Arai Y, Tanzawa Y, et al. KMT2A (MLL) fusions in aggressive sarcomas in young adults. Histopathology. 2019;75(4):508–516. doi: 10.1111/his.13926
   PubMed Web of Science ®Google Scholar
• Rao RC, Dou Y. Hijacked in cancer: The KMT2 (MLL) family of methyltransferases. Nat Rev Cancer. 2015;15(6):334–346. doi: 10.1038/nrc3929
   PubMed Web of Science ®Google Scholar
• Dangi CBS, Firodiya A. Triple-negative breast cancer and it’s therapeutic options. Int J Pharma Bio Sci. 2012;3(2):130–160.
   Google Scholar
• Cho HJ, Kim JT, Baek KE, et al. ‘Regulation of Rho GTPases by RhoGDIs in human cancers’. Cells. 2019 Sep 01;8(9):1037. MDPI. doi: 10.3390/cells8091037
   PubMed Web of Science ®Google Scholar
• Thiel AT, Blessington P, Zou T, et al. MLL-AF9-induced leukemogenesis requires coexpression of the wild-type MLL Allele. Cancer Cell. 2010 Feb;17(2):148–159. doi: 10.1016/j.ccr.2009.12.034
   PubMed Web of Science ®Google Scholar
• Ye X, Zhang R, Lian F, et al. The identification of novel small-molecule inhibitors targeting WDR5-MLL1 interaction through fluorescence polarization based high-throughput screening. Bioorg Med Chem Lett. 2019 Feb;29(4):638–645. doi: 10.1016/j.bmcl.2018.12.035
   PubMed Web of Science ®Google Scholar
• Carugo A, Genovese G, Seth S, et al. In vivo functional platform targeting patient-derived xenografts identifies WDR5-myc association as a critical determinant of pancreatic cancer. Cell Rep. 2016 Jun;16(1):133–147. doi: 10.1016/j.celrep.2016.05.063
   PubMed Web of Science ®Google Scholar
• Weinert T, Huwiler SG, Kung JW, et al. Structural basis of enzymatic benzene ring reduction. Nat Chem Biol. 2015 Aug;11(8):586–591. doi: 10.1038/nchembio.1849
   PubMed Web of Science ®Google Scholar