Cytoplasmic Actin Mutations in Hematological Cancers: Comparison
Please note this is a comparison between Version 2 by Rita Xu and Version 1 by Christophe Ampe.

Cytoplasmic actins are abundant molecules in non-muscle cells, including white blood cells. Two forms exist which are referred to as beta- or gamma-cytoplasmic actin encoded by

ACTB

and

ACTG1

, respectively. They form the building blocks of the dynamic actin polymers of the cytoskeleton that are involved in migration and motility processes of cells. Whereas mutations in cytoplasmic actins have been discovered in congenital diseases, their prevalence in cancer types has not been studied in detail. We show that within hematological cancer cytoplasmic actin mutations occur with higher frequency in two specific subtypes. Beta-actin mutations occur mainly in the subtype diffuse large B-cell lymphoma or DLBCL whereas gamma-actin mutations occur mainly in multiple myeloma. Mapping these mutations on the three dimensional structure reveals they map to regions of actin that are important in actin polymer formation and, for gamma-actin also for myosin interaction. Given their occurrence in these functionally important regions, their role as potential driver mutations or in disease progression merits further investigation.

  • ACTB
  • ACTG1
  • F-actin
  • plasma cell myeloma
  • lymphoid cancer
  • actin mutations
  • meta-analysis of patient data
  • myosin
  • patient cancer data
Please wait, diff process is still running!

References

  1. Lohr, J.G.; Stojanov, P.; Lawrence, M.S.; Auclair, D.; Chapuy, B.; Sougnez, C.; Cruz-Gordillo, P.; Knoechel, B.; Asmann, Y.W.; Slager, S.L.; et al.et al Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing. Proceedings of the National Academy of Sciences 2012, 109, 3879-3884, 10.1073/pnas.1121343109.
  2. Lohr, J.G.; Stojanov, P.; Carter, S.L.; Cruz-Gordillo, P.; Lawrence, M.S.; Auclair, D.; Sougnez, C.; Knoechel, B.; Gould, J.; Saksena, G.; et al.et al Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy. Cancer Cell 2014, 25, 91-101, 10.1016/j.ccr.2013.12.015.
  3. Lohr, J.G.; Stojanov, P.; Carter, S.L.; Cruz-Gordillo, P.; Lawrence, M.S.; Auclair, D.; Sougnez, C.; Knoechel, B.; Gould, J.; Saksena, G.; et al.et al Identification of novel mutational drivers reveals oncogene dependencies in multiple myeloma. Blood 2018, 132, 587-597, 10.1182/blood-2018-03-840132.
  4. Walker, B.A.; Mavrommatis, K.; Wardell, C.P.; Cody Ashby, T.; Bauer, M.; Davies, F.E.; Rosenthal, A.; Wang, H.; Qu, P.; Hoering, A.; et al.et al Identification of novel mutational drivers reveals oncogene dependencies in multiple myeloma. Blood 2018, 132, 587-597, 10.1182/blood-2018-03-840132.
  5. Maura, F.; Bolli, N.; Angelopoulos, N.; Dawson, K.J.; Leongamornlert, D.; Martincorena, I.; Mitchell, T.J.; Fullam, A.; Gonzalez, S.; Szalat, R.; et al.et al Genomic landscape and chronological reconstruction of driver events in multiple myeloma. Nat. Commun. 2019, 10, 3835, 10.1101/388611.
  6. Reddy, A.; Zhang, J.; Davis, N.S.; Moffitt, A.B.; Love, C.L.; Waldrop, A.; Leppa, S.; Pasanen, A.; Meriranta, L.; Karjalainen-Lindsberg, M.L.; et al.et al Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma. Cell 2017, 171, 481-494, 10.1016/j.cell.2017.09.027.
  7. Chapuy, B.; Stewart, C.; Dunford, A.J.; Kim, J.; Kamburov, A.; Redd, R.A.; Lawrence, M.S.; Roemer, M.G.M.; Li, A.J.; Ziepert, M.; et al.et al Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nature Medicine 2018, 24, 679-690, 10.1038/s41591-018-0016-8.
  8. Ampe, C.; Van Troys, M. Mammalian actins: Isoform-specific functions and diseases. In The Actin Cytoskeleton: Handbook of Experimental Pharmacology; Jockusch, B., Ed.; Springer: Cham, Switzerland, 2017; Volume 235, pp. 1–37. ISBN 978-3-319-29806-1.
  9. Laura Witjes; Marleen Van Troys; Joël Vandekerckhove; Klaas Vandepoele; Christophe Ampe; A new evolutionary model for the vertebrate actin family including two novel groups. Molecular Phylogenetics and Evolution 2019, 141, 106632, 10.1016/j.ympev.2019.106632.
  10. Matthew T. Chang; Saurabh Asthana; Sizhi Paul Gao; Byron H. Lee; Jocelyn S. Chapman; Cyriac Kandoth; Jianjiong Gao; Nicholas D. Socci; David B. Solit; Adam B. Olshen; et al.Nikolaus SchultzBarry S. Taylor Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity. Nature Biotechnology 2016, 34, 155-163, 10.1038/nbt.3391.
  11. María Del Mar Maldonado; Suranganie Dharmawardhane; Targeting Rac and Cdc42 GTPases in Cancer. Cancer Research 2018, 78, 3101–3111, 10.1158/0008-5472.can-18-0619.
  12. Jianjiong Gao; Matthew T. Chang; Hannah C. Johnsen; Sizhi Paul Gao; Brooke E. Sylvester; Selcuk Onur Sumer; Hongxin Zhang; David B. Solit; Barry S. Taylor; Nikolaus Schultz; Chris Sander; 3D clusters of somatic mutations in cancer reveal numerous rare mutations as functional targets. Genome Medicine 2017, 9, 4, 10.1186/s13073-016-0393-x.
  13. Sushant Kumar; Declan Clarke; Mark Gerstein; Leveraging protein dynamics to identify cancer mutational hotspots using 3D structures. Proceedings of the National Academy of Sciences 2019, 116, 18962-18970, 10.1073/pnas.1901156116.
  14. Kabsch, W.; Vandekerckhove, J. Structure and function of actin. Annu. Rev. Biophys. Biomol. Struct. 1992, 21, 49–76.
  15. Steven Z. Chou; Thomas D Pollard; Mechanism of actin polymerization revealed by cryo-EM structures of actin filaments with three different bound nucleotides. Proceedings of the National Academy of Sciences 2019, 116, 4265-4274, 10.1073/pnas.1807028115.
  16. Keith R. Willison; The structure and evolution of eukaryotic chaperonin-containing TCP-1 and its mechanism that folds actin into a protein spring. Biochemical Journal 2018, 475, 3009-3034, 10.1042/bcj20170378.
  17. Pollard, T.D; Actin and Actin-Binding Proteins. Cold Spring Harb. Perspect. Biol. 2016, 8, a018226.
  18. Dominguez, R.; Holmes, K.C; Actin Structure and Function. Annu. Rev. Biophys. 2011, 40, 169–186.
  19. Heidi Rommelaere; Davy Waterschoot; Katrien Neirynck; Joël Vandekerckhove; Christophe Ampe; Structural plasticity of functional actin: pictures of actin binding protein and polymer interfaces. Structure 2003, 11, 1279–1289.
  20. Oda, T.; Iwasa, M.; Aihara, T.; Maéda, Y.; Narita, A; The nature of the globular- to fibrous-actin transition. Nature 2009, 457, 441–445.
  21. Fujii, T.; Iwane, A.H.; Yanagida, T.; Namba, K; Direct visualization of secondary structures of F-actin by electron cryomicroscopy. Nature 2010, 467, 724–728.
  22. Kenji Murakami; Takuo Yasunaga; Taro Noguchi; Yuki Gomibuchi; Kien X. Ngo; Taro Q.P. Uyeda; Takeyuki Wakabayashi; Structural Basis for Actin Assembly, Activation of ATP Hydrolysis, and Delayed Phosphate Release. Cell 2010, 143, 275-287, 10.1016/j.cell.2010.09.034.
  23. Vitold E. Galkin; Albina Orlova; Matthijn R. Vos; Gunnar F Schröder; Edward H Egelman; Near-atomic resolution for one state of F-actin. Structure 2015, 23, 173-182, 10.1016/j.str.2014.11.006.
  24. Julian Von Der Ecken; Mirco Müller; William Lehman; Dietmar J. Manstein; Pawel A. Penczek; Stefan Raunser; Structure of the F-actin–tropomyosin complex. Nature 2015, 519, 114-117, 10.1038/nature14033.
  25. Nobuhisa Umeki; Jun Nakajima; Taro Q. P. Noguchi; Kiyotaka Tokuraku; Akira Nagasaki; Kohji Ito; Keiko Hirose; Taro Q.P. Uyeda; Rapid Nucleotide Exchange Renders Asp-11 Mutant Actins Resistant to Depolymerizing Activity of Cofilin, Leading to Dominant Toxicity in Vivo*. Journal of Biological Chemistry 2013, 288, 1739-1749, 10.1074/jbc.M112.404657.
  26. R K Cook; D Root; C Miller; E Reisler; P A Rubenstein; Enhanced stimulation of myosin subfragment 1 ATPase activity by addition of negatively charged residues to the yeast actin NH2 terminus. Journal of Biological Chemistry 1993, 268, 2410–2415.
  27. Carl J. Miller; Wenise W. Wong; Elena Bobkova; Peter Rubenstein; Emil Reisler; Mutational Analysis of the Role of the N Terminus of Actin in Actomyosin Interactions. Comparison with Other Mutant Actins and Implications for the Cross-Bridge Cycle†. Biochemistry 1996, 35, 16557-16565, 10.1021/bi962388+.
  28. K. Sutoh; M. Ando; Y. Y. Toyoshima; Site-directed mutations of Dictyostelium actin: disruption of a negative charge cluster at the N terminus.. Proceedings of the National Academy of Sciences 1991, 88, 7711-7714, 10.1073/pnas.88.17.7711.
  29. Julian Von Der Ecken; Sarah M. Heissler; Salma Pathan-Chhatbar; Dietmar J. Manstein; Stefan Raunser; Cryo-EM structure of a human cytoplasmic actomyosin complex at near-atomic resolution. Nature 2016, 534, 724-728, 10.1038/nature18295.
  30. Sarah M. Heissler; Dietmar J. Manstein; Nonmuscle myosin-2: mix and match. Cellular and Molecular Life Sciences 2013, 70, 1-21, 10.1007/s00018-012-1002-9.
  31. Procaccio, V.; Salazar, G.; Ono, S.; Styers, M.L.; Gearing, M.; Davila, A.; Jimenez, R.; Juncos, J.; Gutekunst, C.-A.; Meroni, G.; et al. A mutation of beta -actin that alters depolymerization dynamics is associated with autosomal dominant developmental malformations, deafness, and dystonia. Am. J. Hum. Genet. 2006, 78, 947–960.
  32. Zhu, M.; Yang, T.; Wei, S.; DeWan, A.T.; Morell, R.J.; Elfenbein, J.L.; Fisher, R.A.; Leal, S.M.; Smith, R.J.H.; Friderici, K.H. Mutations in the γ-Actin Gene (ACTG1) Are Associated with Dominant Progressive Deafness (DFNA20/26). Am. J. Hum. Genet. 2003, 73, 1082–1091.
  33. Van Wijk, E.; Krieger, E.; Kemperman, M.H.; De Leenheer, E.M.R.; Huygen, P.L.M.; Cremers, C.W.R.J.; Cremers, F.P.M.; Kremer, H. A mutation in the gamma actin 1 (ACTG1) gene causes autosomal dominant hearing loss (DFNA20/26). J. Med. Genet. 2003, 40, 879–884.
  34. Matias Morín; Keith E. Bryan; Fernando Mayo; Richard Goodyear; Ángeles Mencía; Silvia Modamio-Høybjør; Ignacio Del Castillo; Jessica M. Cabalka; Guy Richardson; Miguel Ángel Moreno-Pelayo; Peter Rubenstein; Miguel Ángel Moreno-Pelayo; In vivo and in vitro effects of two novel gamma-actin (ACTG1) mutations that cause DFNA20/26 hearing impairment. Human Molecular Genetics 2009, 18, 3075-3089, 10.1093/hmg/ddp249.
  35. Cuvertino, S.; Stuart, H.M.; Chandler, K.E.; Roberts, N.A.; Armstrong, R.; Bernardini, L.; Bhaskar, S.; Callewaert, B.; Clayton-Smith, J.; Davalillo, C.H.; et al.et al Faculty Opinions recommendation of ACTB Loss-of-Function Mutations Result in a Pleiotropic Developmental Disorder. Am. J. Hum. Genet. 2017, 101, 1021–1033, 10.3410/f.732248658.793540344.
  36. Emily Cai; Bryan K. Sun; Audris Chiang; Anna Rogers; Laura Bernet; Binbin Cheng; Joyce Teng; Kerri E. Rieger; Kavita Y. Sarin Md; Postzygotic Mutations in Beta-Actin Are Associated with Becker’s Nevus and Becker’s Nevus Syndrome. Journal of Investigative Dermatology 2017, 137, 1795-1798, 10.1016/j.jid.2017.03.017.
  37. Verloes, A.; Di Donato, N.; Masliah-Planchon, J.; Jongmans, M.; Abdul-Raman, O.A.; Albrecht, B.; Allanson, J.; Brunner, H.; Bertola, D.; Chassaing, N.; et al.et al Baraitser–Winter cerebrofrontofacial syndrome: delineation of the spectrum in 42 cases. European Journal of Human Genetics 2015, 23, 292-301, 10.1038/ejhg.2014.95.
  38. Rivière, J.-B.B.; Van Bon, B.W.M.M.; Hoischen, A.; Kholmanskikh, S.S.; O’Roak, B.J.; Gilissen, C.; Gijsen, S.; Sullivan, C.T.; Christian, S.L.; Abdul-Rahman, O.A.; et al.et al De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome. Nature Genetics 2012, 44, 440–444, 10.1038/ng.1091.
  39. Latham, S.L.; Ehmke, N.; Reinke, P.Y.A.; Taft, M.H.; Eicke, D.; Reindl, T.; Stenzel, W.; Lyons, M.J.; Friez, M.J.; Lee, J.A.; et al.et al Author Correction: Variants in exons 5 and 6 of ACTB cause syndromic thrombocytopenia. Nature Communications 2018, 9, 4930, 10.1038/s41467-018-07404-6.
  40. Latham, S.L.; Ehmke, N.; Reinke, P.Y.A.; Taft, M.H.; Eicke, D.; Reindl, T.; Stenzel, W.; Lyons, M.J.; Friez, M.J.; Lee, J.A.; et al.et al Author Correction: Variants in exons 5 and 6 of ACTB cause syndromic thrombocytopenia. Nature Communications 2018, 9, 4930, 10.1038/s41467-018-07404-6.
  41. Nikolas Hundt; Matthias Preller; Olga Swolski; Angella M. Ang; Hans Georg Mannherz; Dietmar J. Manstein; Mirco Müller; Molecular mechanisms of disease-related human ?-actin mutations p.R183W and p.E364K. The FEBS Journal 2014, 281, 5279-5291, 10.1111/febs.13068.
  42. Jennifer J. Johnston; Kuo-Kuang Wen; Kim Keppler-Noreuil; Melissa McKane; Jessica L. Maiers; Alexander Greiner; Julie C. Sapp; Nih Intramural Sequencing Center; Kris A. DeMali; Peter Rubenstein; et al.Leslie G. Biesecker Functional analysis of a de novo ACTB mutation in a patient with atypical Baraitser-Winter syndrome. Human Mutation 2013, 34, 1242–1249, 10.1002/humu.22350.
  43. Keith E. Bryan; Peter Rubenstein; Allele-specific Effects of Human Deafness γ-Actin Mutations (DFNA20/26) on the Actin/Cofilin Interaction*. Journal of Biological Chemistry 2009, 284, 18260-18269, 10.1074/jbc.M109.015818.
  44. Chunmei Guo; Shuqing Liu; Jiasheng Wang; Ming-Zhong Sun; Frederick Greenaway; ACTB in cancer. Clinica Chimica Acta 2013, 417, 39-44, 10.1016/j.cca.2012.12.012.
  45. T Kakunaga; The role of actin alteration in the neoplastic transformation. Gan to kagaku ryoho. Cancer & chemotherapy 1984, 11, 629–637.
  46. J Leavitt; S Y Ng; M Varma; G Latter; S Burbeck; P Gunning; L Kedes; Expression of transfected mutant beta-actin genes: transitions toward the stable tumorigenic state. Molecular and Cellular Biology 1987, 7, 2467-2476, 10.1128/mcb.7.7.2467.
  47. Paola Cianci; Grazia Fazio; Sara Casagranda; Marco Spinelli; Carmelo Rizzari; Gianni Cazzaniga; Angelo Selicorni; Acute myeloid leukemia in Baraitser-Winter cerebrofrontofacial syndrome. American Journal of Medical Genetics Part A 2017, 173, 546-549, 10.1002/ajmg.a.38057.
  48. Minghui He; Lisa S. Westerberg; Congenital Defects in Actin Dynamics of Germinal Center B Cells. Frontiers in Immunology 2019, 10, 296, 10.3389/fimmu.2019.00296.
  49. Ridley, A.J; Rho GTPase signalling in cell migration. Curr. Opin. Cell Biol. 2015, 36, 103–112.
More
ScholarVision Creations