Regulation of marginal zone B cell development by MINT, a suppressor of Notch/RBP-J signaling pathway.
We found that Msx2-interacting nuclear target protein (MINT) competed with the intracellular region of Notch for binding to a DNA binding protein RBP-J and suppressed the transactivation activity of Notch signaling. Although MINT null mutant mice were embryonic lethal, MINT-deficient splenic B cells differentiated about three times more efficiently into marginal zone B cells with a concomitant reduction of follicular B cells. MINT is expressed in a cell-specific manner: high in follicular B cells and low in marginal zone B cells. Since Notch signaling directs differentiation of marginal zone B lymphocytes and suppresses that of follicular B lymphocytes in mouse spleen, the results indicate that high levels of MINT negatively regulate Notch signaling and block differentiation of precursor B cells into marginal zone B cells. MINT may serve as a functional homolog of Drosophila Hairless.
Kuroda
Kazuki
K
Department of Medical Chemistry, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501, Japan.
Han
Hua
H
Tani
Shoichi
S
Tanigaki
Kenji
K
Tun
Tin
T
Furukawa
Takahisa
T
Taniguchi
Yoshihito
Y
Kurooka
Hisanori
H
Hamada
Yoshio
Y
Toyokuni
Shinya
S
Honjo
Tasuku
T
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D015815:Cell Adhesion Molecules; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins; D018390:Gene Targeting; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D008099:Liver / Q000166:cytology / Q000196:embryology; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D016601:RNA-Binding Proteins; D051880:Receptors, Notch; D015398:Signal Transduction; D015533:Transcriptional Activation
D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D008565:Membrane Proteins; C497759:N protein, Drosophila; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C497571:Rbpj protein, mouse; D051880:Receptors, Notch; C121253:Spen protein, mouse; C498473:X11L protein, Drosophila