Overlap between signal transduction pathways contributing to LMNA laminopathies (Homo sapiens)

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CREBBPP/CAF3232Prelamin-A61C473, 7, 3349473859475818243147, 4842, 5525, 2654Skeletal Dysplasia/Increased fatty deposits in bone marrowTerminal Differentiation-Impaired expansion/ differentiationof WAT+ feedbackMis-localisation to the ERWnt target genesClonal ExpansionHuman MSCRISC ComplexLamin A intranuclear fociAdipocyte ProgenitorOsteogenic genesIncreased stimulation of the + feedback mechanism in ZMPSTE -/- cellsAcetyl Group?Notch target genesUbiquitin mediatedproteasome degredationProliferationRb Proteasomal Degredation?G1/ S phase transition6010404540Osteoblast ProgenitorP21MyostatinMAN1TGFB1SMAD2NOTCH1SMAD3BMP2JUNBWNT7BMIRLET7B47292015Wnt Signaling26S Proteasome Degredation13, 50GSK3BCSNK1A1CTNNB1CSNK1A1LAPCAXIN1CTNNB1CTNNB1LEF1TCF7TCF7L2TCF7L1CTNNB1aaXNull mutationsCaaX group15 amino acidsZMPSTE24Prelamin-ALMNA61Isoprenylcysteine carboxyl methyltransferase CFarnesyltransferaseCaaX group61Prelamin-AZMPSTE24CLamin A61Co-localisationSREBP1cMIR33B3449Prelamin-ASREBP1c27SREBP SignalingRestrictive Dermopathy17, 30Truncated Prelamin-A8HMGA2TLE1Hutchinson-Gilford Progeria SyndromeHES1HES5ProgerinNotch Signaling12Dunnigan-Type Familial Partial LipodystrophyCH3Process with unknown interacting molecules PhosphateUbiquitinFarnesyl GroupLaminopathic signalingEmerinCTNNB1WNT10B56PPARGCEBPACEBPD57CEBPB15Adipocyte genesAdipogenic Stimulieg. GlutocorticoidsPrelamin-AAGO2TARBP2DICER137MIR33B491myogenic differentiationDilated Cardiomyopathy28, 53G1 PhaseOverexpression of proteins involved in oxtidative metabolism19Tissue fibrosis in straited muscle36Mandibuloacral Dysplasia A44S Phaseincreased osteoclastogenesis/ osteoblast differentiation/ex matrix remodellingCell stimulationImpaired myoblast differentiation/Myofibre degenerationMyogenic differentiationtargets Decreased nuclear stability/ abnormal morphology/impaired mechanotransduction/decreased cytoskeletal stiffnessCardiomyocyte16, 23Cytoskeleton43Sacromeres52Altered lamin A Akt mediated phosphorylation/degredation44Rho mediated actin polymerisationPreadipocyte senescence1, 1419Muscle fibersMyocyte Progenitor52Histonesmechanical forcecell cycle Biochemical block/Apoptosis24Akt/mTOR signalingDNAROSContractile impairmentMyofibre defectsCell death41PI3K-AKT-mTOR signaling pathway 44MYOD1Emery Dreifuss Muscular DystrophyOsteoprotegerinMAOB41Oxidative damageNAP1L1RB147Cathepsin K44TGFB253MAOAMAPK/ERK signaling22CDK448Arrhythmogenic RightVentricular Cardiomyopathy/Dilated CardiomyopathyHDAC1MYOD1HistonesRB15MAPK/ERK signaling22LINC complex1121Actinprelamin ACanonical NF-KB pathway23ApoptosisLamin ATGFB signaling516RUNX240TGFB signalingEmerin394MAN1LAP2Alamin AEmerinPPARG35NUCLEAR LAMINA Lamin ALamin ANOTCH NICDEmerin---SPP146Terminal DifferentiationMYOD1E2F1S phase proteins ApoptosisE2F1P/CAFHDAC1RB1HDAC1E2F1


Description

Differentiating hMSC's follow specific lineages depending on the interacting signals recieved from different pathways. Mutations to several genes; focusing of LMNA mutations result in diseases termed laminopathies. These diseases have a number of overlapping phenotypes and are thus often seen as symptoms of each other. This pathway highlights the differentiation of hMSC's into either adipocytes, osteoblasts and myocytes and the altered function of several signaling pathways as a result of laminopathic mutations.

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Bibliography

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  1. Martínez-Balbás MA, Bauer UM, Nielsen SJ, Brehm A, Kouzarides T; ''Regulation of E2F1 activity by acetylation.''; EMBO J, 2000 PubMed Europe PMC Scholia
  2. Muchir A, Pavlidis P, Decostre V, Herron AJ, Arimura T, Bonne G, Worman HJ; ''Activation of MAPK pathways links LMNA mutations to cardiomyopathy in Emery-Dreifuss muscular dystrophy.''; J Clin Invest, 2007 PubMed Europe PMC Scholia
  3. De Boer J, Wang HJ, Van Blitterswijk C; ''Effects of Wnt signaling on proliferation and differentiation of human mesenchymal stem cells.''; Tissue Eng, 2004 PubMed Europe PMC Scholia
  4. Menazza S, Blaauw B, Tiepolo T, Toniolo L, Braghetta P, Spolaore B, Reggiani C, Di Lisa F, Bonaldo P, Canton M; ''Oxidative stress by monoamine oxidases is causally involved in myofiber damage in muscular dystrophy.''; Hum Mol Genet, 2010 PubMed Europe PMC Scholia
  5. Van Berlo JH, Voncken JW, Kubben N, Broers JL, Duisters R, van Leeuwen RE, Crijns HJ, Ramaekers FC, Hutchison CJ, Pinto YM; ''A-type lamins are essential for TGF-beta1 induced PP2A to dephosphorylate transcription factors.''; Hum Mol Genet, 2005 PubMed Europe PMC Scholia
  6. Pekovic V, Harborth J, Broers JL, Ramaekers FC, van Engelen B, Lammens M, von Zglinicki T, Foisner R, Hutchison C, Markiewicz E; ''Nucleoplasmic LAP2alpha-lamin A complexes are required to maintain a proliferative state in human fibroblasts.''; J Cell Biol, 2007 PubMed Europe PMC Scholia
  7. Aberle H, Bauer A, Stappert J, Kispert A, Kemler R; ''beta-catenin is a target for the ubiquitin-proteasome pathway.''; EMBO J, 1997 PubMed Europe PMC Scholia
  8. Bakay M, Wang Z, Melcon G, Schiltz L, Xuan J, Zhao P, Sartorelli V, Seo J, Pegoraro E, Angelini C, Shneiderman B, Escolar D, Chen YW, Winokur ST, Pachman LM, Fan C, Mandler R, Nevo Y, Gordon E, Zhu Y, Dong Y, Wang Y, Hoffman EP; ''Nuclear envelope dystrophies show a transcriptional fingerprint suggesting disruption of Rb-MyoD pathways in muscle regeneration.''; Brain, 2006 PubMed Europe PMC Scholia
  9. Guo L, Li X, Tang QQ; ''Transcriptional regulation of adipocyte differentiation: a central role for CCAAT/enhancer-binding protein (C/EBP) β.''; J Biol Chem, 2015 PubMed Europe PMC Scholia
  10. Bakay M, Wang Z, Melcon G, Schiltz L, Xuan J, Zhao P, Sartorelli V, Seo J, Pegoraro E, Angelini C, Shneiderman B, Escolar D, Chen YW, Winokur ST, Pachman LM, Fan C, Mandler R, Nevo Y, Gordon E, Zhu Y, Dong Y, Wang Y, Hoffman EP; ''Nuclear envelope dystrophies show a transcriptional fingerprint suggesting disruption of Rb-MyoD pathways in muscle regeneration.''; Brain, 2006 PubMed Europe PMC Scholia
  11. Van Berlo JH, Voncken JW, Kubben N, Broers JL, Duisters R, van Leeuwen RE, Crijns HJ, Ramaekers FC, Hutchison CJ, Pinto YM; ''A-type lamins are essential for TGF-beta1 induced PP2A to dephosphorylate transcription factors.''; Hum Mol Genet, 2005 PubMed Europe PMC Scholia
  12. Wang X, Sato R, Brown MS, Hua X, Goldstein JL; ''SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis.''; Cell, 1994 PubMed Europe PMC Scholia
  13. Lloyd DJ, Trembath RC, Shackleton S; ''A novel interaction between lamin A and SREBP1: implications for partial lipodystrophy and other laminopathies.''; Hum Mol Genet, 2002 PubMed Europe PMC Scholia
  14. Lloyd DJ, Trembath RC, Shackleton S; ''A novel interaction between lamin A and SREBP1: implications for partial lipodystrophy and other laminopathies.''; Hum Mol Genet, 2002 PubMed Europe PMC Scholia
  15. Mal A, Sturniolo M, Schiltz RL, Ghosh MK, Harter ML; ''A role for histone deacetylase HDAC1 in modulating the transcriptional activity of MyoD: inhibition of the myogenic program.''; EMBO J, 2001 PubMed Europe PMC Scholia
  16. Ostlund C, Bonne G, Schwartz K, Worman HJ; ''Properties of lamin A mutants found in Emery-Dreifuss muscular dystrophy, cardiomyopathy and Dunnigan-type partial lipodystrophy.''; J Cell Sci, 2001 PubMed Europe PMC Scholia
  17. Lee KS, Hong SH, Bae SC; ''Both the Smad and p38 MAPK pathways play a crucial role in Runx2 expression following induction by transforming growth factor-beta and bone morphogenetic protein.''; Oncogene, 2002 PubMed Europe PMC Scholia
  18. Sinensky M, Fantle K, Trujillo M, McLain T, Kupfer A, Dalton M; ''The processing pathway of prelamin A.''; J Cell Sci, 1994 PubMed Europe PMC Scholia
  19. Peinado JR, Quirós PM, Pulido MR, Mariño G, Martínez-Chantar ML, Vázquez-Martínez R, Freije JM, López-Otín C, Malagón MM; ''Proteomic profiling of adipose tissue from Zmpste24-/- mice, a model of lipodystrophy and premature aging, reveals major changes in mitochondrial function and vimentin processing.''; Mol Cell Proteomics, 2011 PubMed Europe PMC Scholia
  20. Price NL, Holtrup B, Kwei SL, Wabitsch M, Rodeheffer M, Bianchini L, Suárez Y, Fernández-Hernando C; ''SREBP-1c/MicroRNA 33b Genomic Loci Control Adipocyte Differentiation.''; Mol Cell Biol, 2016 PubMed Europe PMC Scholia
  21. Lammerding J, Schulze PC, Takahashi T, Kozlov S, Sullivan T, Kamm RD, Stewart CL, Lee RT; ''Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction.''; J Clin Invest, 2004 PubMed Europe PMC Scholia
  22. Lombardi ML, Lammerding J; ''Keeping the LINC: the importance of nucleocytoskeletal coupling in intracellular force transmission and cellular function.''; Biochem Soc Trans, 2011 PubMed Europe PMC Scholia
  23. Sun T, Fu M, Bookout AL, Kliewer SA, Mangelsdorf DJ; ''MicroRNA let-7 regulates 3T3-L1 adipogenesis.''; Mol Endocrinol, 2009 PubMed Europe PMC Scholia
  24. Lombardi ML, Lammerding J; ''Keeping the LINC: the importance of nucleocytoskeletal coupling in intracellular force transmission and cellular function.''; Biochem Soc Trans, 2011 PubMed Europe PMC Scholia
  25. Lee KS, Hong SH, Bae SC; ''Both the Smad and p38 MAPK pathways play a crucial role in Runx2 expression following induction by transforming growth factor-beta and bone morphogenetic protein.''; Oncogene, 2002 PubMed Europe PMC Scholia
  26. Brack AS, Conboy IM, Conboy MJ, Shen J, Rando TA; ''A temporal switch from notch to Wnt signaling in muscle stem cells is necessary for normal adult myogenesis.''; Cell Stem Cell, 2008 PubMed Europe PMC Scholia
  27. Lee B, Lee TH, Shim J; ''Emerin suppresses Notch signaling by restricting the Notch intracellular domain to the nuclear membrane.''; Biochim Biophys Acta Mol Cell Res, 2017 PubMed Europe PMC Scholia
  28. Dechat T, Korbei B, Vaughan OA, Vlcek S, Hutchison CJ, Foisner R; ''Lamina-associated polypeptide 2alpha binds intranuclear A-type lamins.''; J Cell Sci, 2000 PubMed Europe PMC Scholia
  29. De Boer J, Wang HJ, Van Blitterswijk C; ''Effects of Wnt signaling on proliferation and differentiation of human mesenchymal stem cells.''; Tissue Eng, 2004 PubMed Europe PMC Scholia
  30. Van Berlo JH, Voncken JW, Kubben N, Broers JL, Duisters R, van Leeuwen RE, Crijns HJ, Ramaekers FC, Hutchison CJ, Pinto YM; ''A-type lamins are essential for TGF-beta1 induced PP2A to dephosphorylate transcription factors.''; Hum Mol Genet, 2005 PubMed Europe PMC Scholia
  31. Chen, Q, Shou, P, Zhang, L, Xu, C, Zheng, C, Han. Y, Li, W, Huang, Y, Zhang, X, Shao, C, Roberts, A. I, Rabson, A. B, Ren, G, Zhang, Y, Wang, Y, Denhardt, D. T, Shi, Y; ''An Osteopontin-Integrin Interaction Plays a Critical Role in Directing Adipogenesis and Osteogenesis by Mesenchymal Stem Cells''; Stem Cells, 2014 PubMed Europe PMC Scholia
  32. Sciaudone M, Gazzerro E, Priest L, Delany AM, Canalis E; ''Notch 1 impairs osteoblastic cell differentiation.''; Endocrinology, 2003 PubMed Europe PMC Scholia
  33. Pekovic V, Harborth J, Broers JL, Ramaekers FC, van Engelen B, Lammens M, von Zglinicki T, Foisner R, Hutchison C, Markiewicz E; ''Nucleoplasmic LAP2alpha-lamin A complexes are required to maintain a proliferative state in human fibroblasts.''; J Cell Biol, 2007 PubMed Europe PMC Scholia
  34. Price NL, Holtrup B, Kwei SL, Wabitsch M, Rodeheffer M, Bianchini L, Suárez Y, Fernández-Hernando C; ''SREBP-1c/MicroRNA 33b Genomic Loci Control Adipocyte Differentiation.''; Mol Cell Biol, 2016 PubMed Europe PMC Scholia
  35. Hah J, Kim DH; ''Deciphering Nuclear Mechanobiology in Laminopathy.''; Cells, 2019 PubMed Europe PMC Scholia
  36. Evangelisti C, Bernasconi P, Cavalcante P, Cappelletti C, D'Apice MR, Sbraccia P, Novelli G, Prencipe S, Lemma S, Baldini N, Avnet S, Squarzoni S, Martelli AM, Lattanzi G; ''Modulation of TGFbeta 2 levels by lamin A in U2-OS osteoblast-like cells: understanding the osteolytic process triggered by altered lamins.''; Oncotarget, 2015 PubMed Europe PMC Scholia
  37. Luo YB, Mastaglia FL, Wilton SD; ''Normal and aberrant splicing of LMNA.''; J Med Genet, 2014 PubMed Europe PMC Scholia
  38. Markiewicz E, Tilgner K, Barker N, van de Wetering M, Clevers H, Dorobek M, Hausmanowa-Petrusewicz I, Ramaekers FC, Broers JL, Blankesteijn WM, Salpingidou G, Wilson RG, Ellis JA, Hutchison CJ; ''The inner nuclear membrane protein emerin regulates beta-catenin activity by restricting its accumulation in the nucleus.''; EMBO J, 2006 PubMed Europe PMC Scholia
  39. Voronkov A, Krauss S; ''Wnt/beta-catenin signaling and small molecule inhibitors.''; Curr Pharm Des, 2013 PubMed Europe PMC Scholia
  40. Pekovic, V, Harborth, H, Broers, J. L. V, Ramaekers, F. C. S, van Engelen, B, Lammens, M, von Zglinicki, T, Foisner, R, Hutchison, C, Markiewicz, E; ''Nucleoplasmic LAP2alpha-lamin A Complexes Are Required to Maintain a Proliferative State in Human Fibroblasts''; J Cell Biol, 2007 PubMed Europe PMC Scholia
  41. Muchir A, Pavlidis P, Decostre V, Herron AJ, Arimura T, Bonne G, Worman HJ; ''Activation of MAPK pathways links LMNA mutations to cardiomyopathy in Emery-Dreifuss muscular dystrophy.''; J Clin Invest, 2007 PubMed Europe PMC Scholia
  42. Navarro CL, De Sandre-Giovannoli A, Bernard R, Boccaccio I, Boyer A, Geneviève D, Hadj-Rabia S, Gaudy-Marqueste C, Smitt HS, Vabres P, Faivre L, Verloes A, Van Essen T, Flori E, Hennekam R, Beemer FA, Laurent N, Le Merrer M, Cau P, Lévy N; ''Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identify restrictive dermopathy as a lethal neonatal laminopathy.''; Hum Mol Genet, 2004 PubMed Europe PMC Scholia
  43. Scaffidi P, Misteli T; ''Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing.''; Nat Cell Biol, 2008 PubMed Europe PMC Scholia
  44. Melcon G, Kozlov S, Cutler DA, Sullivan T, Hernandez L, Zhao P, Mitchell S, Nader G, Bakay M, Rottman JN, Hoffman EP, Stewart CL; ''Loss of emerin at the nuclear envelope disrupts the Rb1/E2F and MyoD pathways during muscle regeneration.''; Hum Mol Genet, 2006 PubMed Europe PMC Scholia
  45. Bernasconi P, Carboni N, Ricci G, Siciliano G, Politano L, Maggi L, Mongini T, Vercelli L, Rodolico C, Biagini E, Boriani G, Ruggiero L, Santoro L, Schena E, Prencipe S, Evangelisti C, Pegoraro E, Morandi L, Columbaro M, Lanzuolo C, Sabatelli P, Cavalcante P, Cappelletti C, Bonne G, Muchir A, Lattanzi G; ''Elevated TGF β2 serum levels in Emery-Dreifuss Muscular Dystrophy: Implications for myocyte and tenocyte differentiation and fibrogenic processes.''; Nucleus, 2018 PubMed Europe PMC Scholia
  46. Pratt AJ, MacRae IJ; ''The RNA-induced silencing complex: a versatile gene-silencing machine.''; J Biol Chem, 2009 PubMed Europe PMC Scholia
  47. Aberle H, Bauer A, Stappert J, Kispert A, Kemler R; ''beta-catenin is a target for the ubiquitin-proteasome pathway.''; EMBO J, 1997 PubMed Europe PMC Scholia
  48. Hirano H, Matsuura Y; ''Sensing actin dynamics: structural basis for G-actin-sensitive nuclear import of MAL.''; Biochem Biophys Res Commun, 2011 PubMed Europe PMC Scholia
  49. Hegele RA, Cao H, Frankowski C, Mathews ST, Leff T; ''PPARG F388L, a transactivation-deficient mutant, in familial partial lipodystrophy.''; Diabetes, 2002 PubMed Europe PMC Scholia
  50. Ho CY, Jaalouk DE, Vartiainen MK, Lammerding J; ''Lamin A/C and emerin regulate MKL1-SRF activity by modulating actin dynamics.''; Nature, 2013 PubMed Europe PMC Scholia
  51. Voronkov A, Krauss S; ''Wnt/beta-catenin signaling and small molecule inhibitors.''; Curr Pharm Des, 2013 PubMed Europe PMC Scholia
  52. Brack AS, Conboy IM, Conboy MJ, Shen J, Rando TA; ''A temporal switch from notch to Wnt signaling in muscle stem cells is necessary for normal adult myogenesis.''; Cell Stem Cell, 2008 PubMed Europe PMC Scholia
  53. Ramji DP, Foka P; ''CCAAT/enhancer-binding proteins: structure, function and regulation.''; Biochem J, 2002 PubMed Europe PMC Scholia
  54. Holaska JM, Kowalski AK, Wilson KL; ''Emerin caps the pointed end of actin filaments: evidence for an actin cortical network at the nuclear inner membrane.''; PLoS Biol, 2004 PubMed Europe PMC Scholia
  55. Rivas D, Li W, Akter R, Henderson JE, Duque G; ''Accelerated features of age-related bone loss in zmpste24 metalloproteinase-deficient mice.''; J Gerontol A Biol Sci Med Sci, 2009 PubMed Europe PMC Scholia
  56. Akter R, Rivas D, Geneau G, Drissi H, Duque G; ''Effect of lamin A/C knockdown on osteoblast differentiation and function.''; J Bone Miner Res, 2009 PubMed Europe PMC Scholia
  57. Wang X, Sato R, Brown MS, Hua X, Goldstein JL; ''SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis.''; Cell, 1994 PubMed Europe PMC Scholia
  58. Voronkov A, Krauss S; ''Wnt/beta-catenin signaling and small molecule inhibitors.''; Curr Pharm Des, 2013 PubMed Europe PMC Scholia
  59. Christodoulides C, Lagathu C, Sethi JK, Vidal-Puig A; ''Adipogenesis and WNT signalling.''; Trends Endocrinol Metab, 2009 PubMed Europe PMC Scholia
  60. Maraldi NM, Lattanzi G, Cenni V, Bavelloni A, Marmiroli S, Manzoli FA; ''Laminopathies and A-type lamin-associated signalling pathways.''; Adv Enzyme Regul, 2010 PubMed Europe PMC Scholia
  61. Akiyama T; ''Wnt/beta-catenin signaling.''; Cytokine Growth Factor Rev, 2000 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
134355view05:44, 21 July 2024EgonwRemoved template comments
128410view04:42, 4 February 2024EweitzUpgrade legend
128409view04:39, 4 February 2024EweitzModified description
128408view04:38, 4 February 2024EweitzFix typos, standardize case
128407view04:33, 4 February 2024EweitzFix typos, standardize case
123415view11:15, 25 July 2022EgonwMade another three pathways clickable
120399view09:06, 30 November 2021Fehrhartsmall graphical change, boxed pathway nodes
117843view15:15, 22 May 2021EweitzModified title
110990view15:02, 25 June 2020Fehrhartcorrected a few conversions and added states
110605view18:43, 20 May 2020ZoebaroisModified description
110604view18:33, 20 May 2020ZoebaroisModified title
110554view10:20, 18 May 2020ZoebaroisAddition of ? to whether prelamin A disregulates MAO activity- no concrete evidence available
110291view09:33, 2 May 2020EgonwSecond round of manual cleanup
110290view09:26, 2 May 2020EgonwFirst round of manual clean up of the Biopax xml
110289view09:06, 2 May 2020EgonwMore PubMed identifiers
110288view08:51, 2 May 2020EgonwAdded more PubMed identifiers
110287view08:37, 2 May 2020EgonwMore unicode fixes and added missing PubMed identifiers.
110286view08:28, 2 May 2020EgonwFixed more unicode issues
110285view08:18, 2 May 2020EgonwFixed unicode issues in a few references
110284view08:03, 2 May 2020EgonwReplaced secondary ChEBI identifiers with a primary identifiers.
110259view15:23, 30 April 2020EgonwReplaced a secondary ChEBI identifiers with a primary identifier.
110238view15:15, 29 April 2020EgonwNot a mim-conversion
110039view12:01, 14 April 2020ZoebaroisRemoval of interaction between TCF complex to RUNX2

Conversion arrow from MIR33B synthesis to RISC complex Modification of Rb/MyoD pathway in myoblast with addition of new references

Acetyl group in key changed to yellow
109987view07:36, 9 April 2020ZoebaroisReverted to version '07:31, 9 April 2020' by Zoebarois
109986view07:33, 9 April 2020ZoebaroisObject colours changed to grey
109985view07:31, 9 April 2020ZoebaroisOrganelles and cell objects changed to bold
109963view11:36, 8 April 2020ZoebaroisCorrection of farnesyl groups in lamin A processing
109959view08:32, 8 April 2020ZoebaroisProgerin increased stimulation of SPP1 in hMSC Reference added to SPP1 action of CEBP/B inhibition and RUNX2 stimulation
109957view06:41, 8 April 2020Fehrhartfixed unconnected lines
109909view14:17, 6 April 2020ZoebaroisRemoval of HMGA2 complex as was irrelevant to lipodystrophy

addition of'clonal expansion' and 'terminal differentiation' phase during adipogenesis negative regulation of HMGA2/ CEBPA/ PPARG by RISC complex

Reference added to impaired expansion/differentia
109906view11:41, 6 April 2020ZoebaroisReferences added to LNMA processing

BMPS/TGBFB1 singaling molecues added Notch Signaling regulation of GSK3B/ emerin/ NOTCH1 Dilated cardiomyopathy label added

Cell labels changed to progenitor
109878view13:13, 3 April 2020ZoebaroisModified title
109877view13:12, 3 April 2020ZoebaroisConnected the muscular laminopathic transduction pathway to Canconial Wnt signaling

seperated out the pro-adipogenic process from the HMSC and placed it into a differentiating adipocyte

Incorporated a TGF-B/Smad pathway for the expression of RUNX2 and my
109847view10:25, 2 April 2020ZoebaroisOntology Term : 'familial partial lipodystrophy' added !
109846view09:57, 2 April 2020ZoebaroisOntology Term : 'disease pathway' added !
109845view09:56, 2 April 2020ZoebaroisOntology Term : 'cardiomyopathy' added !
109844view09:56, 2 April 2020ZoebaroisOntology Term : 'Emery-Dreifuss muscular dystrophy' added !
109843view09:55, 2 April 2020ZoebaroisOntology Term : 'progeria' added !
109842view09:53, 2 April 2020ZoebaroisNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AGO2GeneProduct27161 (Entrez Gene)
APCGeneProduct324 (Entrez Gene)
AXIN1GeneProduct8312 (Entrez Gene)
ActinGeneProduct60 (Entrez Gene)
ApoptosisPathwayWP254 (WikiPathways)
Arrhythmogenic Right

Ventricular Cardiomyopathy/

Dilated Cardiomyopathy		PathwayWP2118 (WikiPathways)
BMP2GeneProduct650 (Entrez Gene)
CMetaboliteCHEBI:17376 (ChEBI)
CDK4GeneProductENSG00000135446 (Ensembl)
CEBPAGeneProduct1050 (Entrez Gene) is down regulated following overexpression of miR33B
CEBPBGeneProduct1051 (Entrez Gene)
  • activated in early stages of adipogenesis --> activates transcription of PPARG and CEBPA by binding to promoter region in later stages of adipogenesis as are anti mitotic- promote terminal differentiation
  • Type your comment here
CEBPDGeneProduct1052 (Entrez Gene)
CREBBPGeneProduct1387 (Entrez Gene)
  • involved in the acetylation of MYOD1, enabling it to activate myogenic differentiation targets
  • acetylates histones
CSNK1A1GeneProduct1452 (Entrez Gene)
CSNK1A1LGeneProduct122011 (Entrez Gene)
CTNNB1GeneProduct1499 (Entrez Gene)
Canonical NF-KB pathwayPathwayWP4562 (WikiPathways)
Cathepsin KProteinP43235 (Uniprot-TrEMBL)
DICER1GeneProduct23405 (Entrez Gene)
E2F1GeneProduct1869 (Entrez Gene)
EmerinProteinF8WEQ1 (Uniprot-TrEMBL)
EmerinProteinQ5HY57 (Uniprot-TrEMBL)
  • Q133H mutation showed no significant binding to f-actin
  • loss of emerin leads to dysregulation of myoD pathway
Emery Dreifuss Muscular DystrophyPathwayWP4535 (WikiPathways)
FarnesyltransferaseGeneProduct2339 (Entrez Gene)
GSK3BGeneProduct2932 (Entrez Gene)
HDAC1GeneProduct3065 (Entrez Gene)
HES1GeneProduct3280 (Entrez Gene)
HES5GeneProduct388585 (Entrez Gene)
HMGA2GeneProduct8091 (Entrez Gene)
  • chromatin remodeling factor--> important role in the clonal-expansion phase of adipogenesis - may be able to control critical genes involved in cellular proliferation--> loss of HMGA2 impairs adipocyte differentiation
  • overexpression of miR33B caused a significant reduction in HMGA2
  • HMGA2 is induced during the clonal-expansion phase of adipogenesis but reduced following terminal differentiation
  • Type your comment here
Hutchinson-Gilford Progeria SyndromePathwayWP4320 (WikiPathways)
Isoprenylcysteine carboxyl methyltransferase GeneProduct23463 (Entrez Gene)
JUNBGeneProduct3726 (Entrez Gene)
LAP2AGeneProduct7112 (Entrez Gene)
LEF1GeneProduct51176 (Entrez Gene)
LMNAGeneProduct4000 (Entrez Gene) Single point mutations = AD-EMD
Lamin AGeneProduct4000 (Entrez Gene)
MAN1ProteinQ9Y2U8 (Uniprot-TrEMBL)
MAOAGeneProduct4128 (Entrez Gene)
MAOBGeneProduct4129 (Entrez Gene)
MAPK/ERK signalingPathwayWP1845 (WikiPathways)
MIR33BGeneProduct693120 (Entrez Gene)
MIRLET7BGeneProduct406884 (Entrez Gene) targets HMGA2, decreasing it --> high amounts in mature adipocytes
MYOD1GeneProduct4654 (Entrez Gene)
MyostatinGeneProduct2660 (Entrez Gene)
NAP1L1GeneProduct4673 (Entrez Gene) removes acetylated histones providing an open structure of the chromatin
NOTCH NICDGeneProduct4851 (Entrez Gene)
NOTCH1GeneProduct4851 (Entrez Gene)
Notch SignalingPathwayWP268 (WikiPathways)
OsteoprotegerinGeneProduct4982 (Entrez Gene) anti-osteoclastogenic cytokine
Oxidative damagePathwayWP3941 (WikiPathways)
P/CAFGeneProduct8850 (Entrez Gene)
P21GeneProduct1026 (Entrez Gene)
PI3K-AKT-mTOR signaling pathway PathwayWP3844 (WikiPathways)
PPARGGeneProduct5468 (Entrez Gene) Novel F388L mutation is associated with a form of partial lipodystrophy
Prelamin-AProteinD6RB20 (Uniprot-TrEMBL)
ProgerinGeneProduct4000 (Entrez Gene)
RB1GeneProduct5925 (Entrez Gene)
RUNX2GeneProduct860 (Entrez Gene)
SMAD2GeneProduct4087 (Entrez Gene)
SMAD3GeneProduct4088 (Entrez Gene)
SPP1GeneProduct6696 (Entrez Gene)
SREBP SignalingPathwayWP1982 (WikiPathways)
SREBP1cGeneProduct6720 (Entrez Gene)
TARBP2GeneProduct6895 (Entrez Gene)
TCF7GeneProduct6932 (Entrez Gene)
TCF7L1GeneProduct83439 (Entrez Gene)
TCF7L2GeneProduct6934 (Entrez Gene)
TGFB signalingPathwayWP2742 (WikiPathways)
  • overexpression = tissue fibrosis
  • lmna null/ mutated = deregulation of TGFB/smad pathway
TGFB1GeneProduct7040 (Entrez Gene)
TGFB2GeneProduct7042 (Entrez Gene)
  • lmna H222P mutation - modified interaction with TGFB2 - activation of Akt/mTOR signaling
  • is elavated in EDMD
TLE1GeneProduct7088 (Entrez Gene)
Truncated Prelamin-AProteinD6RB20 (Uniprot-TrEMBL)
  • LMNA heterozygous splicing mutation --> loss of exon 11 results in a truncated pre lamin A - removal of Carboxyl terminal motif - interaction with other proteins - disrupted function
  • can also result from ZMPSTE24 mutations - premature stop codon - no propper processing of lamin A - can also result from null mutations
WNT10BGeneProduct7480 (Entrez Gene) upregulation will stimulate wnt signaling to down regulate adipogenesis
WNT7BGeneProduct7477 (Entrez Gene)
Wnt SignalingPathwayWP428 (WikiPathways)
ZMPSTE24GeneProduct10269 (Entrez Gene)
lamin AGeneProduct4000 (Entrez Gene)
  • mutated lamin A- impairements with emerin bidning - involved in its mislocalisation
  • lmna mutation R527H/ farnesylated laminA = MADA - increased TGFB2
prelamin AGeneProduct4000 (Entrez Gene)
  • mutated lamin A- impairements with emerin bidning - involved in its mislocalisation
  • lmna mutation R527H/ farnesylated laminA = MADA - increased TGFB2

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP4879"
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