Role of N-end rule ubiquitin ligases UBR1 and UBR2 in regulating the leucine-mTOR signaling pathway.
AuthorsKume K, Iizumi Y, Shimada M, Ito Y, Kishi T, Yamaguchi Y, Handa H,
JournalGenes Cells
PubMed ID20298436
'Of 20 natural amino acids, leucine is particularly important for promoting cellular protein synthesis. The effect of leucine involves mammalian target of rapamycin (mTOR), a key protein kinase controlling cell growth. Leucine enhances mTOR-mediated phosphorylation of S6K1 and 4E-BP, thereby promoting protein synthesis. However, how the presence of leucine is ... More
ARD1 stabilization of TSC2 suppresses tumorigenesis through the mTOR signaling pathway.
AuthorsKuo HP, Lee DF, Chen CT, Liu M, Chou CK, Lee HJ, Du Y, Xie X, Wei Y, Xia W, Weihua Z, Yang JY, Yen CJ, Huang TH, Tan M, Xing G, Zhao Y, Lin CH, Tsai SF, Fidler IJ, Hung MC,
JournalSci Signal
PubMed ID20145209
'Mammalian target of rapamycin (mTOR) regulates various cellular functions, including tumorigenesis, and is inhibited by the tuberous sclerosis 1 (TSC1)-TSC2 complex. Here, we demonstrate that arrest-defective protein 1 (ARD1) physically interacts with, acetylates, and stabilizes TSC2, thereby repressing mTOR activity. The inhibition of mTOR by ARD1 inhibits cell proliferation and ... More
TBC1D7 is a third subunit of the TSC1-TSC2 complex upstream of mTORC1.
The tuberous sclerosis complex (TSC) tumor suppressors form the TSC1-TSC2 complex, which limits cell growth in response to poor growth conditions. Through its GTPase-activating protein (GAP) activity toward Rheb, this complex inhibits the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1), a key promoter of cell growth. Here, we identify ... More
Hepatitis B virus X protein upregulates mTOR signaling through IKKß to increase cell proliferation and VEGF production in hepatocellular carcinoma.
AuthorsYen CJ, Lin YJ, Yen CS, Tsai HW, Tsai TF, Chang KY, Huang WC, Lin PW, Chiang CW, Chang TT,
JournalPLoS One
PubMed ID22848663
Hepatocellular carcinoma (HCC), a major cause of cancer-related death in Southeast Asia, is frequently associated with hepatitis B virus (HBV) infection. HBV X protein (HBx), encoded by a viral non-structural gene, is a multifunctional regulator in HBV-associated tumor development. We investigated novel signaling pathways underlying HBx-induced liver tumorigenesis and found ... More