Influence of laminopathies on Wnt signaling (WP4844)

The current pathway represents the different molecular interactions that may occur following the dis-regulation of signaling pathways involved in adipocyte differentiation and proliferation which may result in the abnormal distribution of white adipose tissue, leading to the onset of lipodystrophic syndromes. This laminopathic pathway stems from mutations mainly occuring in the LMNA gene can be associated with the onset of other laminopathic syndromes due to a malfunction in the lamin A processing pathway.Other laminopathic diseases are associated with LMNA mutations, thus this pathway represents the overlapping interactions involved in such phenotypic diseases.
last edited


Zoebarois, L Dupuis, Fehrhart, Egonw, Eweitz, and Finterly

Cited In


Homo sapiens


Rare Diseases


Pathway Ontology: disease pathway

Disease Ontology: progeria


Label Type Compact Identifier
SLC2A4 GeneProduct ncbigene:6517
Adiponectin Protein uniprot:Q15848
MIRLET7B GeneProduct ncbigene:406884
CCND1 GeneProduct ncbigene:595
Wnt Signaling Pathway wikipathways:WP428
Wnt Signaling Pathway wikipathways:WP428
PPAR-γ GeneProduct ncbigene:5468
CEBPD GeneProduct ncbigene:1052
CEBPB GeneProduct ncbigene:1051
CEBPA GeneProduct ncbigene:1050
WNT10B GeneProduct ncbigene:7480
GSK3B GeneProduct ncbigene:2932
CSNK1A1 GeneProduct ncbigene:1452
CTNNB1 GeneProduct ncbigene:1499
CSNK1A1L GeneProduct ncbigene:122011
APC GeneProduct ncbigene:324
AXIN1 GeneProduct ncbigene:8312
CTNNB1 GeneProduct ncbigene:1499
CTNNB1 GeneProduct ncbigene:1499
LEF1 GeneProduct ncbigene:51176
TCF7 GeneProduct ncbigene:6932
TCF7L2 GeneProduct ncbigene:6934
TCF7L1 GeneProduct ncbigene:83439
CTNNB1 GeneProduct ncbigene:1499
ZMPSTE24 GeneProduct ncbigene:10269
Prelamin-A Protein uniprot:D6RB20
LMNA GeneProduct ncbigene:4000
Isoprenylcysteine carboxyl methyltransferase GeneProduct ncbigene:23463
C Metabolite chebi:17376
Farnesyltransferase GeneProduct ncbigene:2339
Prelamin-A Protein uniprot:D6RB20
Prelamin-A Protein uniprot:D6RB20
Prelamin-A Protein uniprot:D6RB20
C Metabolite chebi:17376
ZMPSTE24 GeneProduct ncbigene:10269
C Metabolite chebi:17376
Mature lamin A GeneProduct ncbigene:4000
SREBP1c GeneProduct ncbigene:6720
MIR33B GeneProduct ncbigene:693120
Prelamin-A Protein uniprot:D6RB20
Prelamin-A Protein uniprot:D6RB20
SREBP1c GeneProduct ncbigene:6720
PPARG GeneProduct ncbigene:5468
SREBP Signaling Pathway wikipathways:WP1982
Truncated Prelamin-A Protein uniprot:D6RB20
CDK6 GeneProduct ncbigene:1021
AGO2 GeneProduct ncbigene:27161
TARBP2 GeneProduct ncbigene:6895
HMGA2 GeneProduct ncbigene:8091
DICER1 GeneProduct ncbigene:23405
MIR33B GeneProduct ncbigene:693120
SPP1 GeneProduct ncbigene:6696
RUNX2 GeneProduct ncbigene:860
TLE1 GeneProduct ncbigene:7088
Hutchinson-Gilford Progeria Syndrome Pathway wikipathways:WP4320
HES1 GeneProduct ncbigene:3280
HES5 GeneProduct ncbigene:388585
Progerin GeneProduct ncbigene:4000
Notch Signaling Pathway wikipathways:WP268
EMD GeneProduct ncbigene:2010
Emerin Protein uniprot:F8WEQ1
CTNNB1 GeneProduct ncbigene:1499
Emerin Protein uniprot:F8WEQ1
Emerin Protein uniprot:F8WEQ1
TOR1AIP1 GeneProduct ncbigene:26092
Mature lamin A GeneProduct ncbigene:4000


  1. Wang X, Sato R, Brown MS, Hua X, Goldstein JL. SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis. Cell. 1994 Apr 8;77(1):53–62. PubMed Europe PMC Scholia
  2. Sinensky M, Fantle K, Trujillo M, McLain T, Kupfer A, Dalton M. The processing pathway of prelamin A. J Cell Sci. 1994 Jan;107 ( Pt 1):61–7. PubMed Europe PMC Scholia
  3. Aberle H, Bauer A, Stappert J, Kispert A, Kemler R. beta-catenin is a target for the ubiquitin-proteasome pathway. EMBO J. 1997 Jul 1;16(13):3797–804. PubMed Europe PMC Scholia
  4. Clements L, Manilal S, Love DR, Morris GE. Direct interaction between emerin and lamin A. Biochem Biophys Res Commun. 2000 Jan 27;267(3):709–14. PubMed Europe PMC Scholia
  5. Ross SE, Hemati N, Longo KA, Bennett CN, Lucas PC, Erickson RL, et al. Inhibition of adipogenesis by Wnt signaling. Science. 2000 Aug 11;289(5481):950–3. PubMed Europe PMC Scholia
  6. Akiyama T. Wnt/beta-catenin signaling. Cytokine Growth Factor Rev. 2000 Dec;11(4):273–82. PubMed Europe PMC Scholia
  7. 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 Apr 1;11(7):769–77. PubMed Europe PMC Scholia
  8. Ramji DP, Foka P. CCAAT/enhancer-binding proteins: structure, function and regulation. Biochem J. 2002 Aug 1;365(Pt 3):561–75. PubMed Europe PMC Scholia
  9. Hegele RA, Cao H, Frankowski C, Mathews ST, Leff T. PPARG F388L, a transactivation-deficient mutant, in familial partial lipodystrophy. Diabetes. 2002 Dec;51(12):3586–90. PubMed Europe PMC Scholia
  10. De Boer J, Wang HJ, Van Blitterswijk C. Effects of Wnt signaling on proliferation and differentiation of human mesenchymal stem cells. Tissue Eng. 2004;10(3–4):393–401. PubMed Europe PMC Scholia
  11. Navarro CL, De Sandre-Giovannoli A, Bernard R, Boccaccio I, Boyer A, Geneviève D, et al. Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identify restrictive dermopathy as a lethal neonatal laminopathy. Hum Mol Genet. 2004 Oct 15;13(20):2493–503. PubMed Europe PMC Scholia
  12. Markiewicz E, Tilgner K, Barker N, van de Wetering M, Clevers H, Dorobek M, et al. The inner nuclear membrane protein emerin regulates beta-catenin activity by restricting its accumulation in the nucleus. EMBO J. 2006 Jul 26;25(14):3275–85. PubMed Europe PMC Scholia
  13. Christodoulides C, Lagathu C, Sethi JK, Vidal-Puig A. Adipogenesis and WNT signalling. Trends Endocrinol Metab. 2009 Jan;20(1):16–24. PubMed Europe PMC Scholia
  14. Ling L, Nurcombe V, Cool SM. Wnt signaling controls the fate of mesenchymal stem cells. Gene. 2009 Mar 15;433(1–2):1–7. PubMed Europe PMC Scholia
  15. Sun T, Fu M, Bookout AL, Kliewer SA, Mangelsdorf DJ. MicroRNA let-7 regulates 3T3-L1 adipogenesis. Mol Endocrinol. 2009 Jun;23(6):925–31. PubMed Europe PMC Scholia
  16. Pratt AJ, MacRae IJ. The RNA-induced silencing complex: a versatile gene-silencing machine. J Biol Chem. 2009 Jul 3;284(27):17897–901. PubMed Europe PMC Scholia
  17. Voronkov A, Krauss S. Wnt/beta-catenin signaling and small molecule inhibitors. Curr Pharm Des. 2013;19(4):634–64. PubMed Europe PMC Scholia
  18. Guo L, Li X, Tang Q-Q. Transcriptional regulation of adipocyte differentiation: a central role for CCAAT/enhancer-binding protein (C/EBP) β. J Biol Chem. 2015 Jan 9;290(2):755–61. PubMed Europe PMC Scholia
  19. Price NL, Holtrup B, Kwei SL, Wabitsch M, Rodeheffer M, Bianchini L, et al. SREBP-1c/MicroRNA 33b Genomic Loci Control Adipocyte Differentiation. Mol Cell Biol. 2016 Feb 1;36(7):1180–93. PubMed Europe PMC Scholia