Affiliation: University of Florida
Shan J, Dudenhausen E, Kilberg M. Induction of early growth response gene 1 (EGR1) by endoplasmic reticulum stress is mediated by the extracellular regulated kinase (ERK) arm of the MAPK pathways. Biochim Biophys Acta Mol Cell Res. 2018;: pubmed publisher
..This research highlights the importance of MAPK signaling in response to ER stress and identifies ELK1 as a transcriptional mediator and the EGR1 gene as a target. ..
Shan J, Donelan W, Hayner J, Zhang F, Dudenhausen E, Kilberg M. MAPK signaling triggers transcriptional induction of cFOS during amino acid limitation of HepG2 cells. Biochim Biophys Acta. 2015;1853:539-48 pubmed publisher
..This research identified cFOS as a target of the AAR and further highlights the importance of AA-responsive MAPK signaling in HepG2 cells. ..
Sacharow S, Dudenhausen E, Lomelino C, Rodan L, El Achkar C, Olson H, et al
. Characterization of a novel variant in siblings with Asparagine Synthetase Deficiency. Mol Genet Metab. 2018;123:317-325 pubmed publisher
..Collectively, the results suggest that the Arg49Gln variant affects the enzymatic function of ASNS. The clinical, cellular, and molecular observations from these siblings expand the known phenotypic spectrum of ASD. ..
Kilberg M, Terada N, Shan J. Influence of Amino Acid Metabolism on Embryonic Stem Cell Function and Differentiation. Adv Nutr. 2016;7:780S-9S pubmed publisher
Shan J, Zhang F, Sharkey J, Tang T, Ord T, Kilberg M. The C/ebp-Atf response element (CARE) location reveals two distinct Atf4-dependent, elongation-mediated mechanisms for transcriptional induction of aminoacyl-tRNA synthetase genes in response to amino acid limitation. Nucleic Acids Res. 2016;44:9719-9732 pubmed
..Protein pull-down assays indicated that Atf4 directly interacts with CDK9 and its associated protein cyclin T1. The results demonstrate that AA availability modulates the ARS gene family through modulation of transcription elongation. ..
Hayner J, Shan J, Kilberg M. Regulation of the ATF3 gene by a single promoter in response to amino acid availability and endoplasmic reticulum stress in human primary hepatocytes and hepatoma cells. Biochim Biophys Acta Gene Regul Mech. 2018;1861:72-79 pubmed publisher
..Collectively, the results document that ATF3 expression in normal and transformed human liver originates from the canonical promoter A that responds to multiple stress signals. ..
Kilberg M, Barbosa Tessmann I. Genomic sequences necessary for transcriptional activation by amino acid deprivation of mammalian cells. J Nutr. 2002;132:1801-4 pubmed
..Whereas chop expression is associated with cell stress and apoptosis, activation of the AS gene by ER stress indicates that asparagine may also be critical for cellular processes other than protein synthesis. ..
Kilberg M, Shan J, Su N. ATF4-dependent transcription mediates signaling of amino acid limitation. Trends Endocrinol Metab. 2009;20:436-43 pubmed publisher
..Therefore, understanding the transcriptional programs initiated by amino acid limitation is crucial and timely. ..
Shan J, Balasubramanian M, Donelan W, Fu L, Hayner J, Lopez M, et al
. A mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)-dependent transcriptional program controls activation of the early growth response 1 (EGR1) gene during amino acid limitation. J Biol Chem. 2014;289:24665-79 pubmed publisher
..Collectively, these data document a novel AA-activated MEK-ERK-ELK1 signaling mechanism. ..