Catabolism of skeletal muscle in cachexia (Homo sapiens)

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71716158101115119161010141251511113161661710178310416217LegendProteasome degradationPathwayTranscription-translationStimulationInhibitionNF-kB complexRELACEBPBIL6RMAPK11RPTORPI3KNFKB2NFKB1SMAD4FBXO32IGF1RTNFProtein synthesisPDK1IGF1SMAD3NFKBIAFOXO3IKBKGIL1R1IL6MLST8CPX-3269TNFRSF12AMAP1LC3ATNFRSF1AIL1BSTAT3TNFSF12EP300IKBKBAKT1JAK1Autophagy lysosomal systemAKT1S1MTORRELBMSTNSMAD2IL1ATRIM63RELACVR2ACHUKTRIM63FBXO32MAP1LC3ACPX-503Binding or modificationComplexIndirect stimulationComplex identifierGene productIndirect binding


Description

Cancer related cachexia is a metabolic disease that is defined by an increased breakdown of muscle protein. Muscle breakdown in cachexia occurs mostly due to activation of either the ubiquitin proteasome system, or the autophagy lysosomal system. In this pathway an overview is presented of the different mechanisms that have been found to activate these two systems involved in muscle degradation.

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Bibliography

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  1. Peris-Moreno D, Taillandier D, Polge C; ''MuRF1/TRIM63, Master Regulator of Muscle Mass.''; Int J Mol Sci, 2020 PubMed Europe PMC Scholia
  2. Mammucari C, Milan G, Romanello V, Masiero E, Rudolf R, Del Piccolo P, Burden SJ, Di Lisi R, Sandri C, Zhao J, Goldberg AL, Schiaffino S, Sandri M; ''FoxO3 controls autophagy in skeletal muscle in vivo.''; Cell Metab, 2007 PubMed Europe PMC Scholia
  3. Ross S, Hill CS; ''How the Smads regulate transcription.''; Int J Biochem Cell Biol, 2008 PubMed Europe PMC Scholia
  4. Cai D, Frantz JD, Tawa NE Jr, Melendez PA, Oh BC, Lidov HG, Hasselgren PO, Frontera WR, Lee J, Glass DJ, Shoelson SE; ''IKKbeta/NF-kappaB activation causes severe muscle wasting in mice.''; Cell, 2004 PubMed Europe PMC Scholia
  5. Enwere EK, Lacasse EC, Adam NJ, Korneluk RG; ''Role of the TWEAK-Fn14-cIAP1-NF-κB Signaling Axis in the Regulation of Myogenesis and Muscle Homeostasis.''; Front Immunol, 2014 PubMed Europe PMC Scholia
  6. Gomes MD, Lecker SH, Jagoe RT, Navon A, Goldberg AL; ''Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy.''; Proc Natl Acad Sci U S A, 2001 PubMed Europe PMC Scholia
  7. Joulia-Ekaza D, Cabello G; ''The myostatin gene: physiology and pharmacological relevance.''; Curr Opin Pharmacol, 2007 PubMed Europe PMC Scholia
  8. Sandri M, Sandri C, Gilbert A, Skurk C, Calabria E, Picard A, Walsh K, Schiaffino S, Lecker SH, Goldberg AL; ''Foxo transcription factors inducethe atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy.''; Cell, 2004 PubMed Europe PMC Scholia
  9. Antonia RJ, Karelehto E, Toriguchi K, Matli M, Warren RS, Pfeffer LM, Donner DB; ''STAT3 regulates inflammatory cytokine production downstream of TNFR1 by inducing expression of TNFAIP3/A20.''; J Cell Mol Med, 2022 PubMed Europe PMC Scholia
  10. Schiaffino S, Dyar KA, Ciciliot S, Blaauw B, Sandri M; ''Mechanisms regulating skeletal muscle growth and atrophy.''; FEBS J, 2013 PubMed Europe PMC Scholia
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History

View all...
CompareRevisionActionTimeUserComment
134347view14:32, 20 July 2024EweitzImprove alignment
134346view14:31, 20 July 2024EweitzTailor node dimensions, economize layout
134345view14:26, 20 July 2024EweitzEconomize layout
134344view14:23, 20 July 2024EweitzStandardize pathway node shape
134343view14:21, 20 July 2024EweitzRefine legend
134342view13:54, 20 July 2024EweitzOntology Term : 'cell of skeletal muscle' added !
134221view09:11, 17 July 2024EgonwNormalized the Complex Portal data source
134220view09:10, 17 July 2024EgonwRemoved redundant newlines
134219view09:08, 17 July 2024EgonwRemoved duplicate descriptions.
134111view13:50, 20 June 2024NberkOrganisational reworks
134109view21:13, 18 June 2024NberkChanges to legend
134108view08:40, 18 June 2024NberkCorrected SMAD interactions
134102view14:54, 17 June 2024NberkUpdated legend and references
134101view20:48, 16 June 2024NberkExtended legend
134096view12:27, 15 June 2024NberkCorrected title
134091view14:21, 13 June 2024NberkAdded legend
133928view14:21, 12 June 2024NberkSmall design adjustments
133896view11:23, 12 June 2024NberkAdded mTORC1 identifier
132354view13:49, 6 June 2024NberkSMAD2 identifier and small changes to the layout
131842view13:08, 4 June 2024NberkChanged comments to MAPK11 and CPX-3269
131840view10:12, 4 June 2024NberkReverted to version '12:08, 31 May 2024' by Nberk
131839view10:12, 4 June 2024NberkReverted to version '14:01, 29 May 2024' by Nberk
131838view10:10, 4 June 2024NberkReverted to version '23:41, 30 May 2024' by Nberk
130965view12:08, 31 May 2024NberkModified description
130876view23:41, 30 May 2024EweitzModified title
130670view14:01, 29 May 2024NberkOntology Term : 'cancer pathway' added !
130669view14:01, 29 May 2024NberkOntology Term : 'signaling pathway' added !
130668view13:59, 29 May 2024NberkOntology Term : 'muscle cell' added !
130667view13:59, 29 May 2024NberkOntology Term : 'cancer' added !
130666view13:58, 29 May 2024NberkOntology Term : 'disease pathway' added !
130663view13:51, 29 May 2024NberkNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ACVR2AGeneProductENSG00000121989 (Ensembl)
AKT1GeneProductENSG00000142208 (Ensembl)
AKT1S1GeneProductENSG00000204673 (Ensembl)
Autophagy lysosomal systemPathwayWP4923 (WikiPathways)
CEBPBGeneProductENSG00000172216 (Ensembl)
CHUKGeneProductENSG00000213341 (Ensembl)
CPX-3269ComplexCPX-3269 (Complex Portal)
CPX-503ComplexCPX-503 (Complex Portal)
EP300ProteinENSG00000100393 (Ensembl)
FBXO32ProteinENSG00000156804 (Ensembl)
FOXO3GeneProductENSG00000118689 (Ensembl)
IGF1GeneProductENSG00000017427 (Ensembl)
IGF1RGeneProductENSG00000140443 (Ensembl)
IKBKBGeneProductENSG00000104365 (Ensembl)
IKBKGGeneProductENSG00000269335 (Ensembl)
IL1AGeneProductENSG00000115008 (Ensembl)
IL1BGeneProductENSG00000125538 (Ensembl)
IL1R1GeneProductENSG00000115594 (Ensembl)
IL6GeneProductENSG00000136244 (Ensembl)
IL6RGeneProductENSG00000160712 (Ensembl)
JAK1GeneProductENSG00000162434 (Ensembl)
MAP1LC3AProteinENSG00000101460 (Ensembl)
MAPK11 GeneProductENSG00000185386 (Ensembl) p38beta MAPK
MLST8GeneProductENSG00000167965 (Ensembl)
MSTNGeneProductENSG00000138379 (Ensembl)
MTORGeneProductENSG00000198793 (Ensembl)
NF-kB complex Complex
NFKB1GeneProductENSG00000109320 (Ensembl)
NFKB2GeneProductENSG00000077150 (Ensembl)
NFKBIAGeneProductENSG00000100906 (Ensembl)
PDK1GeneProductENSG00000152256 (Ensembl)
PI3KGeneProductPF00454 (Pfam)
Proteasome degradation PathwayWP183 (WikiPathways)
Protein synthesisPathwayWP107 (WikiPathways)
RELAGeneProductENSG00000173039 (Ensembl)
RELBGeneProductENSG00000104856 (Ensembl)
RELGeneProductENSG00000162924 (Ensembl)
RPTORGeneProductENSG00000141564 (Ensembl)
SMAD2GeneProductENSG00000175387 (Ensembl)
SMAD3GeneProductENSG00000166949 (Ensembl)
SMAD4GeneProductENSG00000141646 (Ensembl)
STAT3GeneProductENSG00000168610 (Ensembl)
TNFGeneProductENSG00000232810 (Ensembl)
TNFRSF12AGeneProductENSG00000006327 (Ensembl)
TNFRSF1AGeneProductENSG00000067182 (Ensembl)
TNFSF12GeneProductENSG00000239697 (Ensembl)
TRIM63 GeneProductENSG00000158022 (Ensembl) MuRF1
TRIM63ProteinENSG00000158022 (Ensembl)

Annotated Interactions

No annotated interactions

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