Inhibition of amino acid-mTOR signaling by a leucine derivative induces G1 arrest in Jurkat cells.
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.
Hidayat
Sujuti
S
Biosignal Research Center, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan.
Yoshino
Ken-ichi
K
Tokunaga
Chiharu
C
Hara
Kenta
K
Matsuo
Masafumi
M
Yonezawa
Kazuyoshi
K
D000409:Alanine / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016193:G1 Phase / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D007930:Leucine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D008715:Methionine / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D018797:Cell Cycle Proteins; C117670:N-acetylleucinamide; D016160:Retinoblastoma Protein; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D008715:Methionine; D011494:Protein Kinases; C546842:MTOR protein, human; C546845:mTOR protein, rat; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D007930:Leucine; D000409:Alanine; D020123:Sirolimus