Biology 101: What is TOR?

Rapamycin, known colloquially as sirolimus, is a macrolide compound used to coat coronary stents, prevent organ transplant rejection, and treat lymphangioleiomyomatosis, a rare lung condition. It has immunosuppressive properties in humans and is particularly beneficial in reducing kidney transplant rejection. (Wikipedia, 2021) In addition, rapamycin suppresses T and B cell activation by decreasing their sensitivity to interleukin-2 (IL-2) via mTOR inhibition. (Wikipedia, 2021). The mTOR inhibition is a mammalian target of rapamycin that links other proteins and is a key component of two unique protein complexes, mTOR complexes 1 and 2, which govern diverse biological processes. ( Lipton, 2015). The mTOR inhibits genes and blocks signaling pathways and has been linked to cancer cell survival signaling. As a result, rapamycin has been widely and rationally used in clinical studies for a variety of malignancies. ( Foster, 2009).

Rapamycin was studied and found to be a noncytotoxic drug that slows tumor proliferation, with evidence of cytostatic action against numerous human malignancies. (Vignot, 2005). Based on numerous preclinical results, trials using rapamycin as an anticancer medication were initiated, and rapamycin analogues with improved pharmacological qualities were produced. (Vignot, 2005). Rapamycin is generated by the soil bacterium streptomyces hygroscopicus and suppresses the immune system. Moreover, rapamycin can be utilized as an antifungal, anti-inflammatory, anti-tumor, and immunosuppressive medication. (Kim, 2014).

Fig. 1. The mTOR Pathway

In mammals, TOR is a main controller of capped mRNA translation. On the contrary, in plants, TOR is a protein kinase, which integrates stress, energy, and nutrient related signals to increase protein synthesis outputs. (Ryabova, 2018). Global translation is regulated by the TOR signaling system. To drive global translational rates in photosynthetic species, the TOR complex integrates a variety of metabolic pathways and environmental inputs. (Ryabova, 2018). Light energy is the most important environmental input, and TOR inactivation reduces light-energy-dependent plant development (Ryabova, 2018). Light, sugar, and brassinosteroid signaling via TOR maintains a balance in plants between hormone-promoted growth and carbon availability (Ryabova, 2018). TOR combines light and metabolic cues to activate apical shoot meristems. Light energy is gathered during photosynthesis to convert carbon input into the creation of sugars that can be used immediately as plant growth material or stored as starch for long-term reserves. (Ryabova, 2018).

As previously stated, TOR has a highly general role in anabolic and catabolic processes in both plants and mammals. TOR expression in seedling and adult plants can be found at a high level in the primary meristems. (Florian, 2011). This shows that, in contrast to mammalian cells, TOR expression is more prevalent in Arabidopsis zones where cell proliferation is related to cytosolic expansion. (Florian, 2011). TOR expression in maize has been found to begin at 12 hours after germination and reach its peak around 48 hours. (Florian, 2011). TOR RNA has also been found to be present at about the same amount in all tissues of 13-day-old seedlings, regardless of stage in development. (Florian, 2011).

The TOR is a master regulator that has been found to be evolutionary conserved in yeasts, plants, animals, and humans. Furthermore, it combines nutrition and energy signals to enhance cell proliferation and growth. (Xiong, 2014). Recent advances in our understanding of the molecular functions and dynamic regulation of the TOR kinase in photosynthetic plants have been made feasible by combining chemical, genetic, and genomic investigations. (Xiong, 2014). However, much remains unknown about how rapamycin and the mTOR pathway are related in plants and how they regulate protein production, influencing functions like photosynthesis.

BY: Tauba Ashrafi

Works Cited

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J, Victoria. “Rapamycin.” Rapamycin - an Overview | ScienceDirect Topics, 2007, www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/rapamycin.

John, Florian, et al. “Plant Tor Signaling Components.” Plant Signaling & Behavior, Landes Bioscience, Nov. 2011, www.ncbi.nlm.nih.gov/pmc/articles/PMC3329340/.

Kim, Yong Hyun, et al. “Production of Rapamycin in Streptomyces Hygroscopicus from Glycerol-Based Media Optimized by Systemic Methodology.” Journal of Microbiology and Biotechnology, U.S. National Library of Medicine, 2014, pubmed.ncbi.nlm.nih.gov/25001557/.

LA;, Schepetilnikov M;Ryabova. “Recent Discoveries on the Role of Tor (Target of Rapamycin) Signaling in Translation in Plants.” Plant Physiology, U.S. National Library of Medicine, 2021, pubmed.ncbi.nlm.nih.gov/29122989/.

Lipton, Jonathan O, and Mustafa Sahin. “The Neurology of Mtor.” Neuron, U.S. National Library of Medicine, 22 Oct. 2014, www.ncbi.nlm.nih.gov/pmc/articles/PMC4223653/.

McCready, Kirsty, et al. “The Importance of Tor Kinase in Plant Development.” Frontiers, Frontiers, 1 Jan. 1AD, www.frontiersin.org/articles/10.3389/fpls.2020.00016/full.

“MTOR.” Wikipedia, Wikimedia Foundation, 8 Oct. 2021, en.wikipedia.org/wiki/MTOR#Inhibition_by_rapamycin.

“Sirolimus.” Wikipedia, Wikimedia Foundation, 4 Oct. 2021, en.wikipedia.org/wiki/Sirolimus.

Xiong, Yan, and Jen Sheen. “The Role of Target of Rapamycin Signaling Networks in Plant Growth and Metabolism.” Plant Physiology, American Society of Plant Biologists, Feb. 2014, www.ncbi.nlm.nih.gov/pmc/articles/PMC3912084/.