Inhibition of amino acid-mTOR signaling by a leucine derivative induces G1 arrest in Jurkat cells.

Abstract	We have previously demonstrated that N-acetylleucine amide, a derivative of L-leucine, inhibits leucine-induced p70(S6k) activation in a rat hepatoma cell line. In the present study, we investigated whether N-acetylleucine amide is capable of inhibiting amino acid-mTOR signaling. N-Acetylleucine amide caused cell cycle arrest at G1 stage in Jurkat cells, a human leukemia T cell line, concomitant with the inhibition of serum-induced p70(S6k) activation and p27 degradation. Treatment of Jurkat cells with this compound also exhibited dephosphorylation of retinoblastoma protein. These effects are similar to the inhibitory effects of rapamycin on amino acid-mTOR signaling pathway and suggest that N-acetylleucine amide acts as a rapamycin-like reagent to inhibit cell cycle progression in Jurkat cells.
Authors	Sujuti Hidayat, Ken-ichi Yoshino, Chiharu Tokunaga, Kenta Hara, Masafumi Matsuo, Kazuyoshi Yonezawa
Journal	Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 301 Issue 2 Pg. 417-23 (Feb 07 2003) ISSN: 0006-291X [Print] United States
PMID	12565877 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antibiotics, Antineoplastic Cell Cycle Proteins N-acetylleucinamide Retinoblastoma Protein Tumor Suppressor Proteins Cyclin-Dependent Kinase Inhibitor p27 Methionine Protein Kinases MTOR protein, human mTOR protein, rat Ribosomal Protein S6 Kinases, 70-kDa TOR Serine-Threonine Kinases Leucine Alanine Sirolimus
Topics	Alanine (chemistry, metabolism) Animals Antibiotics, Antineoplastic (pharmacology) Cell Cycle Proteins (metabolism) Cell Division (physiology) Cyclin-Dependent Kinase Inhibitor p27 G1 Phase (drug effects, physiology) Humans Jurkat Cells Leucine (analogs & derivatives, chemistry, metabolism, pharmacology) Methionine (chemistry, metabolism) Phosphorylation Protein Kinases (metabolism) Retinoblastoma Protein (metabolism) Ribosomal Protein S6 Kinases, 70-kDa (metabolism) Signal Transduction (physiology) Sirolimus (pharmacology) TOR Serine-Threonine Kinases Tumor Suppressor Proteins (metabolism)

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