Beyond Protein Synthesis; The Multifaceted Roles of Tuberin in Cell Cycle Regulation

Abstract

The ability of cells to sense diverse environmental signals, including nutrient availability and conditions of stress, is critical for both prokaryotes and eukaryotes to mount an appropriate physiological response. While there is a great deal known about the different biochemical pathways that can detect and relay information from the environment, how these signals are integrated to control progression through the cell cycle is still an expanding area of research. Over the past three decades the proteins Tuberin, Hamartin and TBC1D7 have emerged as a large protein complex called the Tuberous Sclerosis Complex. This complex can integrate a wide variety of environmental signals to control a host of cell biology events including protein synthesis, cell cycle, protein transport, cell adhesion, autophagy, and cell growth. Worldwide efforts have revealed many molecular pathways which alter Tuberin post-translationally to convey messages to these important pathways, with most of the focus being on the regulation over protein synthesis. Herein we review the literature supporting that the Tuberous Sclerosis Complex plays a critical role in integrating environmental signals with the core cell cycle machinery.

Effects of high-dose folic acid on protein metabolism in breast muscle and performance of broilers

“…S6K1 and eIF4E-binding protein (4EBP1) are the downstream factors of AKT/mTOR pathway, and its activity can be improved by folic acid in a dose-dependent manner ( Pende et al, 2004 ; Hwang et al, 2015 ). In mammalian cell models, S6K1 is a predominantly regulator of cell and body size ( Ruvinsky and Meyuhas, 2006 ; Bonucci et al, 2020 ) and phosphorylates ribosomal protein S6 kinase accelerates the protein synthesis by enhancing the translation initiation ( Wilson et al, 2009 ; Fidalgo et al, 2022 ). In the current study, although no differences were found on mRNA expression and protein abundance of AKT and S6K1 between groups, higher protein expression of p-AKT and p-S6K1 was observed in the folic acid supplementation group.…”

Dissecting the roles of the Tuberin protein in the subcellular localization of the G2/M Cyclin, Cyclin B1

“…Collectively, these data present the possibility that feedback from the Tuberin-CycB1 complex can be provided to regulate G1/S. Hence, Tuberin communicates information about the levels of nutrients, growth factors, and energy stores to the cell cycle machinery to regulate cell division [ 12 – 14 ].…”