Glycogen Synthase Kinase (GSK) 3β Phosphorylates and Protects Nuclear Myosin 1c from Proteasome-Mediated Degradation to Activate rDNA Transcription in Early G1 Cells

English version České info

Nuclear actin and myosin are essential regulators of gene expression. At the exit of mitosis, nuclear myosin 1c (NM1) mediates RNA polymerase I (pol I) transcription activation and cell cycle progression by modulating assembly of the chromatin remodeling complex WICH with the subunits WSTF and SNF2h and, crucially, facilitating H3K9 acetylation by the histone acetyl transferase PCAF. The molecular mechanism by which NM1 is regulated remains however unknown. Here, we conducted a genome-wide screen and demonstrate that GSK3β is selectively coupled to the rDNA transcription unit. In embryonic fibroblasts lacking GSK3β there is a significant drop in rRNA synthesis levels and the rDNA is devoid of actin, NM1 and SNF2h. Concomitantly with a transcriptional block we reveal decreased levels of histone H3 acetylation by the histone acetyl transferase PCAF. At G1, transcriptional repression in the GSK3β knockout mouse embryonic fibroblasts, leads to NM1 ubiquitination by the E3 ligase UBR5 and proteasome-mediated degradation. We conclude that GSK3β suppresses NM1 degradation through the ubiquitin-proteasome system, facilitates NM1 association with the rDNA chromatin and transcription activation at G1. We therefore propose a novel and fundamental role for GSK3β as essential regulator of rRNA synthesis and cell cycle progression.

Vyšlo v časopise: Glycogen Synthase Kinase (GSK) 3β Phosphorylates and Protects Nuclear Myosin 1c from Proteasome-Mediated Degradation to Activate rDNA Transcription in Early G1 Cells. PLoS Genet 10(6): e32767. doi:10.1371/journal.pgen.1004390
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004390

Souhrn

Zdroje

1. GrummtI (2003) Life on a planet of its own: regulation of RNA polymerase I transcription in the nucleolus. Genes Dev 17 : 1691–1702.

2. MossT (2004) At the crossroads of growth control: making ribosomal RNA. Curr Opin Genet Dev 14 : 210–217.

3. RussellJ, ZomerdijkJC (2006) The RNA polymerase I transcription machinery. Biochem Soc Symp 203–216.

4. de LanerolleP, SerebryannyyL (2011) Nuclear actin and myosins: life without filaments. Nat Cell Biol 13 : 1282–1288.

5. VisaN, PercipalleP (2010) Nuclear functions of actin. Cold Spring Harb Perspect Biol 2: a000620.

6. FomproixN, PercipalleP (2004) An actin-myosin complex on actively transcribing genes. Exp Cell Res 294 : 140–148.

7. PhilimonenkoVV, ZhaoJ, IbenS, DingováH, KyseláK, et al. (2004) Nuclear actin and myosin I are required for RNA polymerase I transcription. Nat Cell Biol 6 : 1165–1171.

8. YeJ, ZhaoJ, Hoffmann-RohrerU, GrummtI (2008) Nuclear myosin 1 acts in concert with polymeric actin to drive RNA polymerase I transcription. Genes Dev 22 : 322–330.

9. SarshadA, SadeghifarF, LouvetE, MoriR, BöhmS, et al. (2013) Nuclear myosin 1c facilitates the chromatin modifications required to activate rRNA gene transcription and cell cycle progression. PLoS Genet 9: e1003397.

10. PercipalleP, FomproixN, CavellánE, VoitR, ReimerG, et al. (2006) The chromatin remodelling complex WSTF-SNF2h interacts with nuclear myosin 1 and has a role in RNA polymerase I transcription. EMBO Rep 7 : 525–530.

11. CavellánE, AspP, PercipalleP, Östlund-FarrantsAK (2006) The chromatin remodelling complex WSTF-SNF2h interacts with several nuclear proteins in transcription. J Biol Chem 281 : 16264–16271.

12. VintermistA, BöhmS, SadeghifarF, LouvetE, MansénA, et al. (2011) The chromatin remodeling complex B-WICH changes the chromatin structure and recruits histone acetyl-transferases to active rRNA genes. PLoS One 6: e19184.

13. WoodgettJR (1990) Molecular cloning and expression of glycogen synthase kinase-3/factor A. EMBO J 9 : 2431–2438.

14. WoodgettJR (1991) cDNA cloning and properties of glycogen synthase kinase-3. Methods Enzymol 200 : 564–577.

15. StambolicV, WoodgettJR (1994) Mitogen inactivation of glycogen synthase kinase-3 beta in intact cells via serine 9 phosphorylation. Biochem J 303 : 701–704.

16. WoodgettJR (2001) Judging a protein by more than its name: GSK-3. Sci STKE RE12.

17. WuD, PanW (2010) GSK3: a multifaceted kinase in Wnt signaling. Trends Biochem Sci 35 : 161–168.

18. DingVW, ChenRH, McCormickF (2000) Differential regulation of glycogen synthase kinase 3β by insulin and Wnt signaling. J Biol Chem 275 : 32475–32481.

19. WelckerM, OrianA, JinJ, GrimJE, HarperJW, et al. (2004) The Fbw7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation-dependent c-Myc protein degradation. Proc Natl Acad Sci USA 101 : 9085–9090.

20. RyvesWJ, HarwoodAJ (2003) The interaction of glycogen synthase kinase-3 (GSK-3) with the cell cycle. Prog Cell Cycle Res 5 : 489–495.

21. GrisouardJ, MedunjaninS, HermaniA, ShuklaA, MayerD (2007) Glycogen Synthase Kinase-3 Protects Estrogen Receptor from Proteasomal Degradation and Is Required for Full Transcriptional Activity of the Receptor. Mol Endocrinology 21 : 2427–2439.

22. DryginD, RiceWG, GrummtI (2010) The RNA polymerase I transcription machinery: an emerging target for the treatment of cancer. Annu Rev Pharmacol Toxicol 50 : 131–156.

23. LiuM, TuX, Ferrari-AmorottiG, CalabrettaB, BasergaR (2007) Downregulation of the upstream binding factor1 by glycogen synthase kinase3beta in myeloid cells induced to differentiate. J Cell Biochem 100 : 1154–1169.

24. VincentT, KukalevA, AndängM, PetterssonR, PercipalleP (2008) The glycogen synthase kinase (GSK) 3beta represses RNA polymerase I transcription. Oncogene 27 : 5254–5259.

25. Al-KhouriAM, MaY, TogoSH, WilliamsS, MustelinT (2005) Cooperative phosphorylation of the tumour suppressor phopsphatase and tensin homologue (PTEN) by casein kinases and glycogen synthase kinase 3b. J Biol Chem 280 : 35195–35196.

26. O'SullivanAC, SullivanGJ, McStayB (2002) UBF binding in vivo is not restricted to regulatory sequences within the vertebrate ribosomal DNA repeat. Mol Cell Biol 22 : 657–658.

27. SanijE, PoortingaG, SharkeyK, HungS, HollowayTP, et al. (2008) UBF levels determine the number of active ribosomal RNA genes in mammals. J Cell Biol 183 : 1259–1274.

28. ZentnerGE, SaiakhovaA, ManaenkovP, AdamsMD, ScacheriPC (2011) Integrative genomic analysis of human ribosomal DNA. Nucleic Acids Res 39 : 4949–4960.

29. PercipalleP, LouvetE (2012) In vivo run-on assays to monitor nascent precursor RNA transcripts. Methods Mol Biol 809 : 519–533.

30. MohnF, WeberM, SchübelerD, RoloffTC (2009) Methylated DNA immunoprecipitation (MeDIP). Methods Mol Biol 507 : 55–64.

31. SérandourAA, AvnerS, PercevaultF, DemayF, BizotM, et al. (2011) Epigenetic switch involved in activation of pioneer factor FOXA1-dependent enhancers. Genome Res 21 : 555–565.

32. BoulonS, WestmanBJ, HuttenS, BoisvertFM, LamondAI (2010) The nucleolus under stress. Mol Cell 40 : 216–227.

33. TaelmanVF, DobrowolskiR, PlouhinecJL, FuentealbaLC, VorwaldPP, et al. (2010) Wnt signaling requires sequestration of glycogen synthase kinase 3 inside multivesicular endosomes. Cell 143 : 1136–1148.

34. KinoshitaE, Kinoshita-KikutaE, UjiharaH, KoikeT (2009) Mobility shift detection of phosphorylation on large proteins using a Phos-tag SDS-PAGE gel strengthened with agarose. Proteomics 9 : 4098–4101.

35. RosnerM, SchipanyK, HengstschlägerM (2013) Merging high-quality biochemical fractionation with a refined flow cytometry approach to monitor nucleocytoplasmic protein expression throughout the unperturbed mammalian cell cycle. Nat Protoc 8 : 602–626.

36. ColeA, FrameS, CohenP (2004) Further evidence that the tyrosine phosphorylation of glycogen synthase kinase-3 (GSK) in mammalian cells is an autophosphorylation event. Biochem J 377 : 249–255.

37. MeijerL, SkaltsounisAL, MagiatisP, PolychronopoulosP, KnockaertM, et al. (2003) GSK-3-selective inhibitors derived from Tyrian purple indirubins. Chem Biol 10 : 1255–1266.

38. TsengA-S, EngelFB, KeatingMT (2006) The GSK-3 inhibitor BIO promotes proliferation in mammalian cardiomyocytes. Chem Biol 13 : 957–963.

39. JopeRS, JohnsonGVW (2004) The glamour and gloom of glycogen synthase-3. Trends Biochem Sci 29 : 95–102.

40. FiolCJ, MahrenholzAM, WangY, RoeskeRW, RoachPJ (1987) Formation of protein kinase recognition sites by covalent modification of the substrate. Molecular mechanism for the synergistic action of casein kinase II and glycogen synthase kinase 3. J Biol Chem 262 : 14042–14048.

41. CohenP, FrameS (2001) The renaissance of GSK3. Nat Rev Mol Cell Biol 2 : 769–776.

42. FuentealbaLC, EiversE, IkedaA, HurtadoC, KurodaH, et al. (2007) Integrating patterning signals: Wnt/GSK3 regulates the duration of the BMP/Smad1 signal. Cell 131 : 980–993.

43. KimNG, XuC, GumbinerBM (2009) Identification of targets of the Wnt pathway destruction complex in addition to β-catenin. Proc Natl Acad Sci USA 106 : 5165–5170.

44. Hay-KorenA, CaspiM, Rosin-ArbesfeldR (2011) The EDD E3 ligase ubiquitinates and up-regulates beta-catenin. Mol Biol Cell 22 : 399–411.

45. TasakiT, SriramSM, ParkKS, KwonYT (2012) The N-end rule pathway. Annu Rev Biochem 81 : 261–289.

46. TsaiYC, GrecoTM, BoonmeeA, MitevaY, CristeaIM (2012) Functional proteomics establishes the interaction of SIRT7 with chromatin remodeling complexes and expands its role in regulation of RNA polymerase I transcription. Mol Cell Proteomics 11 : 60–76.

47. MunozMA, SaundersDN, HendersonMJ, ClancyJL, RussellAJ, et al. (2007) The E3 ubiquitin ligase EDD regulates S-phase and G(2)/M DNA damage checkpoints. Cell Cycle 6 : 3070–3077.

48. SmitsVA (2012) EDD induces cell cycle arrest by increasing p53 levels. Cell Cycle 11 : 715–720.

49. BenavidesM, Chow-TsangLF, ZhangJ, ZhongH (2013) The novel interaction between microspherule protein Msp58 and ubiquitin E3 ligase EDD regulates cell cycle progression. Biochim Biophys Acta 1833 : 21–32.

50. YoungDW, HassanMQ, PratapJ, GalindoM, ZaidiSK, et al. (2007) Mitotic occupancy and lineage-specific transcriptional control of rRNA genes by Runx2. Nature 445 : 442–446.