Biology:DDIT4L
 Generic protein structure example |
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.[1][2] The gene is located on chromosome 4 or chromosome 3 in human or mouse respectively.[3][4]
Function
DDIT4L is a negative regulator of mTOR.[5] 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.[6][7][8] Cardiomyocytes showed increase expression of DDIT4L under pathological stress, which promoted autophagy through the inhibition of mTORC1, not mTORC2.[7]
Role in Disease
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.[9] 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.[7]
See also
References
- ↑ "Human PubMed Reference". https://www.ncbi.nlm.nih.gov/protein/NP_660287.1.
- ↑ "Mouse PubMed Reference". https://www.ncbi.nlm.nih.gov/protein/NP_084419.2.
- ↑ "NCBI Reference Sequence: NC_000004.12". 6 April 2022. https://www.ncbi.nlm.nih.gov/nuccore/NC_000004.
- ↑ "NCBI Reference Sequence: NC_000069.6". 24 June 2020. https://www.ncbi.nlm.nih.gov/nuccore/NC_000069.6.
- ↑ "REDD2-mediated inhibition of mTOR promotes dendrite retraction induced by axonal injury". Cell Death and Differentiation 22 (4): 612–25. April 2015. doi:10.1038/cdd.2014.149. PMID 25257176.
- ↑ "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. May 2009. doi:10.1016/j.freeradbiomed.2009.02.020. PMID 19268525.
- ↑ 7.0 7.1 7.2 "DDiT4L promotes autophagy and inhibits pathological cardiac hypertrophy in response to stress". Science Signaling 10 (468). February 2017. doi:10.1126/scisignal.aaf5967. PMID 28246202.
- ↑ "REDD2 gene is upregulated by modified LDL or hypoxia and mediates human macrophage cell death". Arteriosclerosis, Thrombosis, and Vascular Biology 24 (10): 1830–5. October 2004. doi:10.1161/01.ATV.0000142366.69080.c3. PMID 15308555.
- ↑ "Long noncoding RNA H19X is a key mediator of TGF-β-driven fibrosis". The Journal of Clinical Investigation 130 (9): 4888–4905. September 2020. doi:10.1172/JCI135439. PMID 32603313.
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