Abstract
Cell growth is dynamically regulated in response to external cues such as nutrient availability, growth factor signals, and stresses. Central to this adaptation process is the Target of Rapamycin Complex 1 (TORC1), an evolutionarily conserved kinase complex that fine-tunes an enormous number of cellular events. How upstream signals are sensed and transmitted to TORC1 has been intensively studied in major model organisms including the budding yeast Saccharomyces cerevisiae. This field recently saw a breakthrough: the identification of yeast phosphatidylInositol(3)-phosphate binding protein 2 (Pib2) protein as a critical regulator of TORC1. Although the study of Pib2 is still in its early days, multiple groups have provided important mechanistic insights on how Pib2 relays nutrient signals to TORC1. There remain, on the other hand, significant gaps in our knowledge and mysteries that warrant further investigations. This is the first dedicated review on Pib2 that summarizes major findings and outstanding questions around this emerging key player in cell growth regulation.
Highlights
Major Players in Target of Rapamycin Complex 1 (TORC1) RegulationEmerging Master Regulator of YeastWhether uni- or multicellular, all organisms flexibly adapt to their ever-changing environment at the individual cell level
Not surprisingly given the prevalence and importance of processes regulated by this kinase, dysregulation of mammalian/mechanistic TORC1 is associated with many human diseases including cancer, diabetes, and neurodegeneration as well as aging [4]
Lacking either Pib2 or the EGO complex alone causes the entire loss of the acute TORC1 activation by amino acids [35,39], rather than a partial defect that the parallel model would predict
Summary
Whether uni- or multicellular, all organisms flexibly adapt to their ever-changing environment at the individual cell level. The bidirectional nature of TORC1 heterodimer comprised of GDP-loaded Gtr1/RagA/B and GTP-loaded Gtr2/RagC/D inhibits TORC1 This inhibitory regulation is common to yeast and mammals, though the mechanisms appear distinct [27,28]. After excluding proposed TORC1 regulators that have not been extensively studied at a mechanistic level, and remain possible to indirectly affect TORC1 activity either by protecting cells from stresses or by modulating the nutrient uptake, arguably, Rag. GTPases have long been the only well-established, dedicated signaling component that directly and critically regulates TORC1 in yeast. I, summarize in this article major findings and outstanding questions around Pib, to further stimulate future studies on this emerging key player in cell growth regulation
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