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DDIT4L

From Wikipedia, the free encyclopedia
DDIT4L
Identifiers
AliasesDDIT4L, REDD2, Rtp801L, DNA damage inducible transcript 4 like
External IDsOMIM: 607730; MGI: 1920534; HomoloGene: 12698; GeneCards: DDIT4L; OMA:DDIT4L - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_145244

NM_030143

RefSeq (protein)

NP_660287

NP_084419

Location (UCSC)Chr 4: 100.19 – 100.19 MbChr 3: 137.33 – 137.33 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

DNA-damage-inducible transcript 4 like (DDIT4L) or regulated in development and DNA damage response 2 (REDD2) is a protein that in humans is encoded by the DDIT4L gene.[5][6] The gene is located on chromosome 4 or chromosome 3 in human or mouse respectively.[7][8]

Function

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DDIT4L is a negative regulator of mTOR.[9] DDIT4L is a stress responsive protein, its expression is increased under the hypoxic condition and causes or sensitize towards cell death through the regulation mTOR activity and reduction of thioredoxin-1.[10][11][12] Cardiomyocytes showed increase expression of DDIT4L under pathological stress, which promoted autophagy through the inhibition of mTORC1, not mTORC2.[11]

Role in Disease

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In fibrosis, nuclear long noncoding RNA (lncRNA) H19X repressed DDIT4L gene expression, specifically interacting with a region upstream of the DDIT4L gene and increased collagen expression and fibrosis.[13] Expression of DDIT4L is increased in pathological cardiac hypertrophy but not in those of physiological cardiac hypertrophy. Such mice had mild systolic dysfunction, increased baseline autophagy, reduced mTORC1 activity, and increased mTORC2 activity.[11]

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000145358Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000046818Ensembl, 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.
  5. ^ "Human PubMed Reference".
  6. ^ "Mouse PubMed Reference".
  7. ^ "NCBI Reference Sequence: NC_000004.12". 6 April 2022.
  8. ^ "NCBI Reference Sequence: NC_000069.6". 24 June 2020.
  9. ^ Morquette B, Morquette P, Agostinone J, Feinstein E, McKinney RA, Kolta A, Di Polo A (April 2015). "REDD2-mediated inhibition of mTOR promotes dendrite retraction induced by axonal injury". Cell Death and Differentiation. 22 (4): 612–25. doi:10.1038/cdd.2014.149. PMC 4572858. PMID 25257176.
  10. ^ Imen JS, Billiet L, Cuaz-Pérolin C, Michaud N, Rouis M (May 2009). "The regulated in development and DNA damage response 2 (REDD2) gene mediates human monocyte cell death through a reduction in thioredoxin-1 expression". Free Radical Biology & Medicine. 46 (10): 1404–10. doi:10.1016/j.freeradbiomed.2009.02.020. PMID 19268525.
  11. ^ a b c Simonson B, Subramanya V, Chan MC, Zhang A, Franchino H, Ottaviano F, et al. (February 2017). "DDiT4L promotes autophagy and inhibits pathological cardiac hypertrophy in response to stress". Science Signaling. 10 (468). doi:10.1126/scisignal.aaf5967. PMC 5509050. PMID 28246202.
  12. ^ Cuaz-Pérolin C, Furman C, Larigauderie G, Legedz L, Lasselin C, Copin C, et al. (October 2004). "REDD2 gene is upregulated by modified LDL or hypoxia and mediates human macrophage cell death". Arteriosclerosis, Thrombosis, and Vascular Biology. 24 (10): 1830–5. doi:10.1161/01.ATV.0000142366.69080.c3. PMID 15308555. S2CID 17866868.
  13. ^ Pachera E, Assassi S, Salazar GA, Stellato M, Renoux F, Wunderlin A, et al. (September 2020). "Long noncoding RNA H19X is a key mediator of TGF-β-driven fibrosis". The Journal of Clinical Investigation. 130 (9): 4888–4905. doi:10.1172/JCI135439. PMC 7456219. PMID 32603313.