However, the mechanism by which mTORC2 is activated upon interaction with ribosomes still needs to be clarified. Glutaminolysis provides an interesting mTOR-related link between metabolism and cancer. PF-562271 ic50 Highly proliferating cancer cells are often glutamine-addicted, and tumor growth correlates with the activity of glutaminase (GLS), the enzyme that catalyzes the first step of glutaminolysis [123 and 124]. Conversely, inhibition of GLS blocks cancer development and slows growth in certain gliomas [125 and 126]. Duran et al. [ 63••] recently demonstrated that glutaminolysis also activates mTORC1, thereby

promoting cell growth and inhibiting autophagy [ 63••]. These findings suggest that glutaminolysis promotes cancer, at least partly, via mTORC1 activation. Targeting both glutaminolysis and mTORC1 may be a strategy for treatment of glutamine-addicted tumors. This review emphasizes the importance of mTOR signaling in aging, whole body metabolism, and cancer. Tissue-specific mTORC1 and mTORC2 deletions have revealed that each of the two complexes has different

roles in different organs with regard to whole body glucose and lipid homeostasis. For example impaired mTORC2 signaling in the selleck monoclonal humanized antibody inhibitor liver and muscle leads to a diabetic phenotype whereas mTORC2 deletion in adipose tissue does not cause diabetes. Similarly, deletion of mTORC1 signaling in muscle but not in adipose tissue or liver leads to glucose intolerance. Thus, the development of treatments that target mTOR signaling to delay aging or to treat metabolic

disorders and cancer will require understanding tissue-specific mTOR signaling. Even though rapamycin has been shown to increase lifespan and to protect against cancer, side effects such as immunosuppression or diabetes may limit rapamycin’s usefulness as a potential longevity drug. Papers of particular interest, published within the period of review, have been highlighted Adenosine as: • of special interest We acknowledge support from the Swiss National Science Foundation, the Swiss Cancer League, the Louis–Jeantet Foundation, the SFD-ALFEDIAM (MC), the Werner Siemens Foundation (VA) and the Canton of Basel. “
“Current Opinion in Genetics & Development 2013, 23:72–74 Available online 28th Feb 2013 0959-437X/$ – see front matter, © 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.gde.2013.01.006 In animals, early stages of embryo development are associated with extensive epigenetic reprogramming to coordinate zygotic genome activation (ZGA) [2]. ZGA is typically delayed, although to a varying extent depending on the species, with a gradual loss of the maternal dominance and increase of zygotic influence [1 and 2].