Guanine nucleotide exchange factor, Tiam1, directly binds to c-Myc and interferes with c-Myc-mediated apoptosis in rat-1 fibroblasts.
The transcription factor c-Myc is important for the control of cell growth, cell cycle progression, neoplasia, and apoptotic cell death. Recently, c-Myc-binding proteins, which bind either to the N-terminal domain or the C-terminal domain of c-Myc, have been proposed as the key molecules to realize the mechanisms of these multiple c-Myc functions. We report in the present study on another protein, Tiam1, which is a specific guanine nucleotide exchange factor of Rac1 and which binds to c-Myc and modulates several of its biological functions. We were able to detect the direct binding and in vivo association between c-Myc and Tiam1. The necessary role in this interaction of the Myc box II of c-Myc was revealed in the cell extracts. The additional discovery of the intranuclear localization of Tiam1 in Rat1 cells and in neuronal cells of the mouse brain suggests this interaction may occur in the nucleus. Overexpression of Tiam1 repressed the luciferase activity of c-Myc and also inhibited the c-Myc apoptotic activity through this protein-protein interaction. Taken together, we concluded that Tiam1 is another c-Myc regulator, working in the nuclei to control c-Myc-related apoptosis.
Otsuki
Yoshiro
Y
First Department of Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan.
Tanaka
Masamitsu
M
Kamo
Takaharu
T
Kitanaka
Chifumi
C
Kuchino
Yoshiyuki
Y
Sugimura
Haruhiko
H
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D009363:Neoplasm Proteins; D011506:Proteins / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D051381:Rats; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1
D020662:Guanine Nucleotide Exchange Factors; D009363:Neoplasm Proteins; D011506:Proteins; D016271:Proto-Oncogene Proteins c-myc; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C087334:TIAM1 protein, human; C513260:Tiam1 protein, mouse; C513259:Tiam1 protein, rat