Effect of progerin on genes involved in Hutchinson-Gilford progeria syndrome (WP4320)

The effect of progerin on the involved genes in HGPS. Each coloured box shows a different element of the pathway. The red box on the upper right shows that upregulation of the p53 pathway leads to apoptosis and senescence. The box beneath the red one, the purple one, indicates the inhibition of the Wnt pathway by progerin which results in bone abnormalities. The blue box portraits the epigenetic changes done by heterochromatin and euchromatin silencing. The green box shows that progerin activates SKIP which stimulates the Notch signaling pathway. The orange box surrounds the Mi-2/NuRD complex which is depleted by progerin leading mainly to epigenetic changes. The final yellow box shows the inhibition of SERBP1 by progerin resulting in dysfunctional adipose tissue. Legend shows basic and MIM-interactions and indication for methylation.
last edited

Authors

Lorasimons, DeSl, Fehrhart, and Eweitz

Cited In

Organism

Homo sapiens

Communities

Diseases Rare Diseases

Annotations

Pathway Ontology: disease pathway

Disease Ontology: progeria

Participants

Label Type Compact Identifier
Notch signaling Pathway wikipathways:WP268
MBD3 GeneProduct ensembl:ENSG00000071655
LEF1 GeneProduct ensembl:ENSG00000138795
KDM1A GeneProduct ensembl:ENSG00000004487
Progerin Protein uniprot:P02545-6
HDAC2 GeneProduct ensembl:ENSG00000196591
CBX3 GeneProduct ensembl:ENSG00000122565
CHD3 GeneProduct ensembl:ENSG00000170004
RBBP4 GeneProduct ensembl:ENSG00000162521
E2F1 GeneProduct ensembl:ENSG00000101412
p53 pathway Pathway wikipathways:WP3982
Histone H3.3 Protein uniprot:P84243
MBD2 GeneProduct ensembl:ENSG00000134046
CBX1 GeneProduct ensembl:ENSG00000108468
MTA2 GeneProduct ensembl:ENSG00000149480
CHD4 GeneProduct ensembl:ENSG00000111642
HDAC1 GeneProduct ensembl:ENSG00000116478
MTA3 GeneProduct ensembl:ENSG00000057935
SKIP GeneProduct ensembl:ENSG00000132376
Histone H3.2 Protein uniprot:Q71DI3
Histone H3.1 Protein uniprot:P68431
Wnt pathway Pathway wikipathways:WP363
SREBF1 GeneProduct ensembl:ENSG00000072310
Histone H3.2 Protein uniprot:Q71DI3
CBX5 GeneProduct ensembl:ENSG00000094916
Histone H3.3 Protein uniprot:P84243
MTA1 GeneProduct ensembl:ENSG00000182979
Histone H3.1 Protein uniprot:P68431
RBBP7 GeneProduct ensembl:ENSG00000102054
SUV39H1 GeneProduct ensembl:ENSG00000101945
CBX1 GeneProduct ensembl:ENSG00000108468
CBX3 GeneProduct ensembl:ENSG00000122565
CBX5 GeneProduct ensembl:ENSG00000094916
SUV39H1 GeneProduct ensembl:ENSG00000101945
RB1 GeneProduct ensembl:ENSG00000139687
TP53 GeneProduct ensembl:ENSG00000141510

References

  1. Zhang Y, Reinberg D. Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails. Genes Dev. 2001 Sep 15;15(18):2343–60. PubMed Europe PMC Scholia
  2. Goldman RD, Shumaker DK, Erdos MR, Eriksson M, Goldman AE, Gordon LB, et al. Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome. Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):8963–8. PubMed Europe PMC Scholia
  3. Cox LS, Faragher RGA. From old organisms to new molecules: integrative biology and therapeutic targets in accelerated human ageing. Cell Mol Life Sci. 2007 Oct;64(19–20):2620–41. PubMed Europe PMC Scholia
  4. Hernandez L, Roux KJ, Wong ESM, Mounkes LC, Mutalif R, Navasankari R, et al. Functional coupling between the extracellular matrix and nuclear lamina by Wnt signaling in progeria. Dev Cell. 2010 Sep 14;19(3):413–25. PubMed Europe PMC Scholia
  5. Prokocimer M, Barkan R, Gruenbaum Y. Hutchinson-Gilford progeria syndrome through the lens of transcription. Aging Cell. 2013 Aug;12(4):533–43. PubMed Europe PMC Scholia
  6. Daemen S, Kutmon M, Evelo CT. A pathway approach to investigate the function and regulation of SREBPs. Genes Nutr. 2013 May;8(3):289–300. PubMed Europe PMC Scholia
  7. Vidak S, Foisner R. Molecular insights into the premature aging disease progeria. Histochem Cell Biol. 2016 Apr;145(4):401–17. PubMed Europe PMC Scholia
  8. Millard CJ, Varma N, Saleh A, Morris K, Watson PJ, Bottrill AR, et al. The structure of the core NuRD repression complex provides insights into its interaction with chromatin. Elife. 2016 Apr 21;5:e13941. PubMed Europe PMC Scholia
  9. Gonzalo S, Kreienkamp R, Askjaer P. Hutchinson-Gilford Progeria Syndrome: A premature aging disease caused by LMNA gene mutations. Ageing Res Rev. 2017 Jan;33:18–29. PubMed Europe PMC Scholia