DDIT4L

DDIT4L is a negative regulator of mTOR.{{cite journal | vauthors = Morquette B, Morquette P, Agostinone J, Feinstein E, McKinney RA, Kolta A, Di Polo A | title = REDD2-mediated inhibition of mTOR promotes dendrite retraction induced by axonal injury | journal = Cell Death and Differentiation | volume = 22 | issue = 4 | pages = 612–25 | date = April 2015 | pmid = 25257176 | pmc = 4572858 | doi = 10.1038/cdd.2014.149 }} 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.{{cite journal | vauthors = Imen JS, Billiet L, Cuaz-Pérolin C, Michaud N, Rouis M | title = The regulated in development and DNA damage response 2 (REDD2) gene mediates human monocyte cell death through a reduction in thioredoxin-1 expression | journal = Free Radical Biology & Medicine | volume = 46 | issue = 10 | pages = 1404–10 | date = May 2009 | pmid = 19268525 | doi = 10.1016/j.freeradbiomed.2009.02.020 }}{{cite journal | vauthors = Simonson B, Subramanya V, Chan MC, Zhang A, Franchino H, Ottaviano F, Mishra MK, Knight AC, Hunt D, Ghiran I, Khurana TS, Kontaridis MI, Rosenzweig A, Das S | display-authors = 6 | title = DDiT4L promotes autophagy and inhibits pathological cardiac hypertrophy in response to stress | journal = Science Signaling | volume = 10 | issue = 468 | date = February 2017 | pmid = 28246202 | pmc = 5509050 | doi = 10.1126/scisignal.aaf5967 }}{{cite journal | vauthors = Cuaz-Pérolin C, Furman C, Larigauderie G, Legedz L, Lasselin C, Copin C, Jaye M, Searfoss G, Yu KT, Duverger N, Nègre-Salvayre A, Fruchart JC, Rouis M | display-authors = 6 | title = REDD2 gene is upregulated by modified LDL or hypoxia and mediates human macrophage cell death | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 24 | issue = 10 | pages = 1830–5 | date = October 2004 | pmid = 15308555 | doi = 10.1161/01.ATV.0000142366.69080.c3 | s2cid = 17866868 | doi-access = free }} Cardiomyocytes showed increase expression of DDIT4L under pathological stress, which promoted autophagy through the inhibition of mTORC1, not mTORC2.{{cite journal | vauthors = Simonson B, Subramanya V, Chan MC, Zhang A, Franchino H, Ottaviano F, Mishra MK, Knight AC, Hunt D, Ghiran I, Khurana TS, Kontaridis MI, Rosenzweig A, Das S | display-authors = 6 | title = DDiT4L promotes autophagy and inhibits pathological cardiac hypertrophy in response to stress | journal = Science Signaling | volume = 10 | issue = 468 | date = February 2017 | pmid = 28246202 | pmc = 5509050 | doi = 10.1126/scisignal.aaf5967 }}

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.{{cite journal | vauthors = Pachera E, Assassi S, Salazar GA, Stellato M, Renoux F, Wunderlin A, Blyszczuk P, Lafyatis R, Kurreeman F, de Vries-Bouwstra J, Messemaker T, Feghali-Bostwick CA, Rogler G, van Haaften WT, Dijkstra G, Oakley F, Calcagni M, Schniering J, Maurer B, Distler JH, Kania G, Frank-Bertoncelj M, Distler O | display-authors = 6 | title = Long noncoding RNA H19X is a key mediator of TGF-β-driven fibrosis | journal = The Journal of Clinical Investigation | volume = 130 | issue = 9 | pages = 4888–4905 | date = September 2020 | pmid = 32603313 | pmc = 7456219 | doi = 10.1172/JCI135439 }} 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.

• DDIT4/ REDD1
• mTOR
• mTORC1
• mTORC2

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Category:Proteins

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