GDF15

GDF15
Identifiers
Aliases	GDF15, GDF-15, MIC-1, MIC1, NAG-1, PDF, PLAB, PTGFB, growth differentiation factor 15, TGF-PL
External IDs	OMIM: 605312 MGI: 1346047 HomoloGene: 3576 GeneCards: GDF15
Gene location (Human)
Chr.	Chromosome 19 (human)[1]
End	18,389,176 bp[1]
Gene location (Mouse)
Chr.	Chromosome 8 (mouse)[2]
End	70,632,456 bp[2]
RNA expression pattern
	More reference expression data
Gene ontology
Molecular function	• transforming growth factor beta receptor binding; • growth factor activity; • GO:0001948 protein binding; • cytokine activity; • protein homodimerization activity;
Cellular component	• extracellular region; • extracellular exosome; • cell nucleus; • cytoplasm; • extracellular; • Golgi apparatus; • collagen-containing extracellular matrix;
Biological process	• regulation of apoptotic process; • cell-cell signaling; • positive regulation of pathway-restricted SMAD protein phosphorylation; • positive regulation of myoblast fusion; • regulation of MAPK cascade; • transforming growth factor beta receptor signaling pathway; • cell development; • signal transduction; • BMP signaling pathway; • SMAD protein signal transduction; • regulation of receptor activity; • activation of MAPK activity; • reduction of food intake in response to dietary excess; • glial cell-derived neurotrophic factor receptor signaling pathway; • negative regulation of multicellular organism growth; • positive regulation of MAPK cascade; • positive regulation of protein kinase B signaling; • negative regulation of growth hormone receptor signaling pathway;
	Sources:Amigo / QuickGO
Orthologs
	9518
	23886
	ENSG00000130513
	ENSMUSG00000038508
	Q99988
	Q9Z0J7
	NM_004864
	NM_011819; NM_001330687
	NP_004855
	NP_001317616; NP_035949
	Wikidata
View/Edit Human	View/Edit Mouse

Growth/differentiation factor 15 (GDF15) was first identified as Macrophage inhibitory cytokine-1 or MIC-1.[5]

It is a protein belonging to the transforming growth factor beta superfamily. Under normal conditions, GDF-15 is expressed in low concentrations in most organs and upregulated because of injury of organs such as such as liver, kidney, heart and lung.[6][7][8]

The function of GDF-15 is not fully cleared but it seems to have a role in regulating inflammatory pathways and to be involved in regulating apoptosis, cell repair and cell growth, which are biological processes observed in cardiovascular and neoplastic disorders.[6][9][10] GDF-15 has shown to be a strong prognostic protein in patients with different diseases such as heart diseases and cancer.[11]

Metformin was shown to cause increased levels of GDF-15. This increase mediates the effect of body weight loss by metformin.[12]

A monoclonal antibody (mAB1) that neutralizes circulating GDF-15 is being tested in mice and non-human primates as a potential treatment for cancer-related cachexia.[13]

References

GRCh38: Ensembl release 89: ENSG00000130513 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000038508 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
Bootcov MR, Bauskin AR, Valenzuela SM, Moore AG, Bansal M, He XY, et al. (October 1997). "MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily". Proceedings of the National Academy of Sciences of the United States of America. 94 (21): 11514–9. Bibcode:1997PNAS...9411514B. doi:10.1073/pnas.94.21.11514. PMC 23523. PMID 9326641.
Zimmers TA, Jin X, Hsiao EC, McGrath SA, Esquela AF, Koniaris LG (June 2005). "Growth differentiation factor-15/macrophage inhibitory cytokine-1 induction after kidney and lung injury". Shock. 23 (6): 543–8. PMID 15897808.
Hsiao EC, Koniaris LG, Zimmers-Koniaris T, Sebald SM, Huynh TV, Lee SJ (May 2000). "Characterization of growth-differentiation factor 15, a transforming growth factor beta superfamily member induced following liver injury". Molecular and Cellular Biology. 20 (10): 3742–51. doi:10.1128/MCB.20.10.3742-3751.2000. PMC 85678. PMID 10779363.
Ago T, Sadoshima J (February 2006). "GDF15, a cardioprotective TGF-beta superfamily protein". Circulation Research. 98 (3): 294–7. doi:10.1161/01.RES.0000207919.83894.9d. PMID 16484622.
Wollert KC, Kempf T, Lagerqvist B, Lindahl B, Olofsson S, Allhoff T, et al. (October 2007). "Growth differentiation factor 15 for risk stratification and selection of an invasive treatment strategy in non ST-elevation acute coronary syndrome". Circulation. 116 (14): 1540–8. doi:10.1161/CIRCULATIONAHA.107.697714. PMID 17848615.
Kempf T, Eden M, Strelau J, Naguib M, Willenbockel C, Tongers J, et al. (February 2006). "The transforming growth factor-beta superfamily member growth-differentiation factor-15 protects the heart from ischemia/reperfusion injury". Circulation Research. 98 (3): 351–60. doi:10.1161/01.RES.0000202805.73038.48. PMID 16397141.
Wallentin L, Zethelius B, Berglund L, Eggers KM, Lind L, Lindahl B, et al. (2013). "GDF-15 for prognostication of cardiovascular and cancer morbidity and mortality in men". PLOS ONE. 8 (12): e78797. Bibcode:2013PLoSO...878797W. doi:10.1371/journal.pone.0078797. PMC 3846468. PMID 24312445.
Coll AP, Chen M, Taskar P, Rimmington D, Patel S, Tadross J, et al. (December 2019). "GDF15 mediates the effects of metformin on body weight and energy balance". Nature. 578 (7795): 444–448. doi:10.1038/s41586-019-1911-y. PMC 7234839. PMID 31875646.
Wu Z, Bennett D, Brosnan J, Calle RA, Collins S, Esquejo R, et al. (2020). "Growth differentiation factor 15 (GDF-15) neutralization reverses cancer cachexia, restores physical performance and mitigates emesis associated with platinum-based chemotherapy". Annals of Oncology. 31 (suppl_4): S245–S259. doi:10.1016/annonc/annonc265 (inactive 2021-01-14).CS1 maint: DOI inactive as of January 2021 (link)

External links

GDF 15 in Oncology
Overview of all the structural information available in the PDB for UniProt: Q99988 (Growth/differentiation factor 15) at the PDBe-KB.

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000130513 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000038508 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9326641-5] Bootcov MR, Bauskin AR, Valenzuela SM, Moore AG, Bansal M, He XY, et al. (October 1997). "MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily". Proceedings of the National Academy of Sciences of the United States of America. 94 (21): 11514–9. Bibcode:1997PNAS...9411514B. doi:10.1073/pnas.94.21.11514. PMC 23523. PMID 9326641.

[zimmers-6] Zimmers TA, Jin X, Hsiao EC, McGrath SA, Esquela AF, Koniaris LG (June 2005). "Growth differentiation factor-15/macrophage inhibitory cytokine-1 induction after kidney and lung injury". Shock. 23 (6): 543–8. PMID 15897808.

[hsiao-7] Hsiao EC, Koniaris LG, Zimmers-Koniaris T, Sebald SM, Huynh TV, Lee SJ (May 2000). "Characterization of growth-differentiation factor 15, a transforming growth factor beta superfamily member induced following liver injury". Molecular and Cellular Biology. 20 (10): 3742–51. doi:10.1128/MCB.20.10.3742-3751.2000. PMC 85678. PMID 10779363.

[8] Ago T, Sadoshima J (February 2006). "GDF15, a cardioprotective TGF-beta superfamily protein". Circulation Research. 98 (3): 294–7. doi:10.1161/01.RES.0000207919.83894.9d. PMID 16484622.

[9] Wollert KC, Kempf T, Lagerqvist B, Lindahl B, Olofsson S, Allhoff T, et al. (October 2007). "Growth differentiation factor 15 for risk stratification and selection of an invasive treatment strategy in non ST-elevation acute coronary syndrome". Circulation. 116 (14): 1540–8. doi:10.1161/CIRCULATIONAHA.107.697714. PMID 17848615.

[10] Kempf T, Eden M, Strelau J, Naguib M, Willenbockel C, Tongers J, et al. (February 2006). "The transforming growth factor-beta superfamily member growth-differentiation factor-15 protects the heart from ischemia/reperfusion injury". Circulation Research. 98 (3): 351–60. doi:10.1161/01.RES.0000202805.73038.48. PMID 16397141.

[11] Wallentin L, Zethelius B, Berglund L, Eggers KM, Lind L, Lindahl B, et al. (2013). "GDF-15 for prognostication of cardiovascular and cancer morbidity and mortality in men". PLOS ONE. 8 (12): e78797. Bibcode:2013PLoSO...878797W. doi:10.1371/journal.pone.0078797. PMC 3846468. PMID 24312445.

[12] Coll AP, Chen M, Taskar P, Rimmington D, Patel S, Tadross J, et al. (December 2019). "GDF15 mediates the effects of metformin on body weight and energy balance". Nature. 578 (7795): 444–448. doi:10.1038/s41586-019-1911-y. PMC 7234839. PMID 31875646.

[13] Wu Z, Bennett D, Brosnan J, Calle RA, Collins S, Esquejo R, et al. (2020). "Growth differentiation factor 15 (GDF-15) neutralization reverses cancer cachexia, restores physical performance and mitigates emesis associated with platinum-based chemotherapy". Annals of Oncology. 31 (suppl_4): S245–S259. doi:10.1016/annonc/annonc265 (inactive 2021-01-14).CS1 maint: DOI inactive as of January 2021 (link)