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Alias

DDIT4, Dig2, and RTP801, Redd1


Function

redd1 is interesting as Overexpression of REDD1 was sufficient to downregulate mTOR (Growth Control Under Stress: mTOR Regulation through the REDD1-TSC Pathway), a protein which regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, transcription.

redd1 acts as a negative regulator of mTOR, a protein which regulates cell growth, cell proliferation, ...

Flow chart: hypoxia -> redd1 -> tsc2 -> mTorc1 hypoxia related gene - Identification of a Novel Hypoxia-Inducible Factor 1-Responsive Gene, RTP801, Involved in Apoptosis

  • " This gene is ubiquitously expressed in multiple human tissues at low levels. However, in response to hypoxia its transcription is rapidly and sharply increased both in vitro and in vivo."

relation to mTOR via TSC -

  • The Stress-inducted Proteins RTP801 and RTP801L Are Negative Regulators of the Mammalian Target of Rapamycin Pathway - "We show that both RTP801 and RTP801L function as potent negative regulators of the mammalian target of rapamycin. Furthermore, we show that these proteins function upstream of TSC2 and Rheb. Since RTP801 and RTP801L are up-regulated at the transcriptional level in response to a variety of stresses, including DNA damage, hypoxia, and glucocorticoid treatment (23–27), we speculate RTP801 and RTP801L may play critical roles in coupling certain extra- and intracellular cues to the regulation of translation through mTOR."
  • Growth Control Under Stress: mTOR Regulation through the REDD1-TSC Pathway -


Flow chart detail

  • hypoxia upregulates HIF-1
  • HIF-1 upregulates redd1 (Identification of a Novel Hypoxia-Inducible Factor 1-Responsive Gene, RTP801, Involved in Apoptosis)
  • Activates Tsc1/Tsc2 in humans and flies(Regulation of mTOR and Cell Growth in Response to Energy Stress by REDD1, The hypoxia-induced paralogs Scylla and Charybdis inhibit growth by down-regulating S6K activity upstream of TSC in Drosophila). Better cite: Hypoxia regulates TSC1/2–mTOR signaling and tumor suppression through REDD1-mediated 14–3–3 shuttling. mechanism is known
  • Tsc1/Tsc2 inhbits mTORC1


redd1 acts as a negative regulator of mTOR, a protein which regulates cell growth, cell proliferation,.... In particular, upregulation of HIF-1 in response to hypoxia upregulates redd1, leading to activation of Tsc1/Tsc2 and the inhibition of mTORC1. The exact mechanism of redd1's effect on Tsc1/Tsc1 in unclear, but has been observed in both mammals and fly homologues.

Big Picture: hypoxia as tumor suppressor - Hypoxia regulates TSC1/2–mTOR signaling and tumor suppression through REDD1-mediated 14–3–3 shuttling


Function Final

DDIT4/REDD1 acts as a negative regulator of mTOR [1], a serine/threonine kinase that regulates a variety of cellular functions such as growth, proliferation and autophagy [2]. In particular, upregulation of HIF-1 in response to hypoxia upregulates REDD1 [3], leading to activation of Tsc1/2 via 14–3–3 shuttling [4] and subsequent downregulation of mTOR via Rheb [5]

Clinical Significance

Due to its role as a negative regulator of mTOR, redd1 has

See Also

  1. ^ Sofer, A.; Lei, K.; Johannessen, C. M.; Ellisen, L. W. (29 June 2005). "Regulation of mTOR and Cell Growth in Response to Energy Stress by REDD1". Molecular and Cellular Biology. 25 (14): 5834–5845. doi:10.1128/MCB.25.14.5834-5845.2005.
  2. ^ Sato, T; Nakashima, A; Guo, L; Coffman, K; Tamanoi, F (1 March 2010). "Single amino-acid changes that confer constitutive activation of mTOR are discovered in human cancer". Oncogene. 29 (18): 2746–2752. doi:10.1038/onc.2010.28.
  3. ^ Shoshani, T.; Faerman, A.; Mett, I.; Zelin, E.; Tenne, T.; Gorodin, S.; Moshel, Y.; Elbaz, S.; Budanov, A.; Chajut, A.; Kalinski, H.; Kamer, I.; Rozen, A.; Mor, O.; Keshet, E.; Leshkowitz, D.; Einat, P.; Skaliter, R.; Feinstein, E. (1 April 2002). "Identification of a Novel Hypoxia-Inducible Factor 1-Responsive Gene, RTP801, Involved in Apoptosis". Molecular and Cellular Biology. 22 (7): 2283–2293. doi:10.1128/MCB.22.7.2283-2293.2002.
  4. ^ DeYoung, M. P.; Horak, P.; Sofer, A.; Sgroi, D.; Ellisen, L. W. (15 January 2008). "Hypoxia regulates TSC1/2 mTOR signaling and tumor suppression through REDD1-mediated 14 3 3 shuttling". Genes & Development. 22 (2): 239–251. doi:10.1101/gad.1617608.
  5. ^ Inoki, K. (1 August 2003). "Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling". Genes & Development. 17 (15): 1829–1834. doi:10.1101/gad.1110003.
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