Departments of Pharmacology and Pathology, University of California, San Diego, School of Medicine, La Jolla, CA 92093-0723, USA.
Published: June 2016
AI Article Synopsis
Article Abstract
Sestrins are highly conserved, stress-inducible proteins that inhibit target of rapamycin complex 1 (TORC1) signaling. After their transcriptional induction, both vertebrate and invertebrate Sestrins turn on the adenosine monophosphate (AMP)-activated protein kinase (AMPK), which activates the tuberous sclerosis complex (TSC), a key inhibitor of TORC1 activation. However, Sestrin overexpression, on occasion, can result in TORC1 inhibition even in AMPK-deficient cells. This effect has been attributed to Sestrin's ability to bind the TORC1-regulating GATOR2 protein complex, which was postulated to control trafficking of TORC1 to lysosomes. How the binding of Sestrins to GATOR2 is regulated and how it contributes to TORC1 inhibition are unknown. New findings suggest that the amino acid leucine specifically disrupts the association of Sestrin2 with GATOR2, thus explaining how leucine and related amino acids stimulate TORC1 activity. We discuss whether and how these findings fit what has already been learned about Sestrin-mediated TORC1 inhibition from genetic studies conducted in fruit flies and mammals.
The mechanistic target of rapamycin complex 1 (mTORC1) functions as a master regulator of cell growth and proliferation. We previously demonstrated that intracellular calcium ion (Ca) concentration modulates the mTORC1 pathway via binding of the Ca sensor protein calmodulin (CaM) to tuberous sclerosis complex 2 (TSC2), a critical negative regulator of mTORC1. However, the precise molecular mechanism by which Ca/CaM modulates mTORC1 activity remains unclear.
Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
Cell metabolism is crucial for orchestrating the differentiation and function of regulatory T cells (Tregs). However, the underlying mechanism that coordinates cell metabolism to regulate Treg activity is not completely understood. As a pivotal molecule in lipid metabolism, the role of SHIP-1 in Tregs remains unknown.
Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao 266237, China. Electronic address:
Regulatory-associated protein of TOR (RAPTOR) is a key component of TOR complex 1 (TORC1), which determines the lysosomal location and substrate recruitment of TORC1 to promote cell growth and prevent autophagy. Many studies in recent decades have focused on the posttranslational modification of RAPTOR; however, little is known about the transcriptional regulatory mechanism of Raptor. Using the lepidopteran insect cotton bollworm (Helicoverpa armigera) as model, we reveal the transcriptional regulatory mechanism of Raptor.
It has been established that essential amino acids (EAA) regulate protein synthesis in mammary epithelial cells by rapidly altering the phosphorylation state of translation factors. However, the long-term transcriptional response to EAA supply has been investigated much less. Eight transcription factors were selected as candidate mediators of EAA effects on mammary cell function via the amino acid response (ATF4, ATF6), mitogen-activated protein kinase (JUN, FOS, EGR1), and mechanistic target of rapamycin complex 1 (MYC, HIF1A, SREBF1).
Tor kinases play diverse and essential roles in control of nutrient signaling and cell growth. These kinases are assembled into two multiprotein complexes known as TORC1 and TORC2. In budding yeast, TORC2 relays nutrient-dependent signals that strongly influence growth rate and cell size.
