Smad7 is an activin-inducible inhibitor of activin-induced growth arrest and apoptosis in mouse B cells

被引:111
作者
Ishisaki, A
Yamato, K
Nakao, A
Nonaka, K
Ohguchi, M
ten Dijke, P
Nishihara, T
机构
[1] Natl Inst Infect Dis, Dept Oral Sci, Shinjuku Ku, Tokyo 1628640, Japan
[2] Tokyo Med & Dent Univ, Fac Dent, Dept Mol Cellular Oncol Microbiol, Bunkyo Ku, Tokyo 1138549, Japan
[3] Chiba Univ, Sch Med, Dept Med, Chuo Ku, Chiba 2600856, Japan
[4] Biomed Ctr, Ludwig Inst Canc Res, S-75124 Uppsala, Sweden
关键词
D O I
10.1074/jbc.273.38.24293
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Members of the transforming growth factor-p (TGF-P) family, which includes the activins, relay signals from serine/threonine kinase receptors in membrane to nucleus via intracellular Sma- and Mad-related (Smad) proteins. Inhibitory Smad proteins were found to prevent the interaction between the serine/threonine kinase receptors and pathway-restricted Smad proteins. Smad7 was identified as a TGF-beta-inducible antagonist of TGF-beta signaling, and it may participate in a negative feedback loop to control TGF-beta signaling. Here we demonstrate that the mRNA expression of Smad7 is induced by activin A in mouse B cell hybridoma HS-72 cells, which undergo growth arrest and apoptosis upon exposure to activin A. The ectopic expression of mouse Smad7 in HS-72 cells suppressed the activin A-induced cell cycle arrest in the G(1) phase by abolishing the activin A-induced expression of p21(CIP1/WAF1) and hypophosphorylation of retinoblastoma protein. Furthermore, Smad7 expression suppressed activin A-induced apoptosis in HS-72 cells. Thus, our data indicate that Smad7 is an activin A-inducible antagonist of activin A-induced growth arrest and apoptosis of B lineage cells.
引用
收藏
页码:24293 / 24296
页数:4
相关论文
共 43 条
[1]   Increase in Bcl-2 level promoted by CD40 ligation correlates with inhibition of B cell apoptosis induced by vacuolar type H+-ATPase inhibitor [J].
Akifusa, S ;
Ohguchi, M ;
Koseki, T ;
Nara, K ;
Semba, I ;
Yamato, K ;
Okahashi, N ;
Merino, R ;
Núñez, G ;
Hanada, N ;
Takehara, T ;
Nishihara, T .
EXPERIMENTAL CELL RESEARCH, 1998, 238 (01) :82-89
[2]   NOVEL ACTIVIN RECEPTORS - DISTINCT GENES AND ALTERNATIVE MESSENGER-RNA SPLICING GENERATE A REPERTOIRE OF SERINE THREONINE KINASE RECEPTORS [J].
ATTISANO, L ;
WRANA, JL ;
CHEIFETZ, S ;
MASSAGUE, J .
CELL, 1992, 68 (01) :97-108
[3]  
Attisano Liliana, 1996, Cytokine and Growth Factor Reviews, V7, P327, DOI 10.1016/S1359-6101(96)00042-1
[4]   TYPE-I RECEPTORS SPECIFY GROWTH-INHIBITORY AND TRANSCRIPTIONAL RESPONSES TO TRANSFORMING GROWTH-FACTOR-BETA AND ACTIVIN [J].
CARCAMO, J ;
WEIS, FMB ;
VENTURA, F ;
WIESER, R ;
WRANA, JL ;
ATTISANO, L ;
MASSAGUE, J .
MOLECULAR AND CELLULAR BIOLOGY, 1994, 14 (06) :3810-3821
[5]   TGF-beta receptor signaling [J].
Derynck, R ;
Feng, XH .
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 1997, 1333 (02) :F105-F150
[6]   DETERMINATION OF TYPE-I RECEPTOR SPECIFICITY BY THE TYPE-II RECEPTORS FOR TGF-BETA OR ACTIVIN [J].
EBNER, R ;
CHEN, RH ;
LAWLER, S ;
ZIONCHECK, T ;
DERYNCK, R .
SCIENCE, 1993, 262 (5135) :900-902
[7]   PURIFICATION AND CHARACTERIZATION OF ERYTHROID-DIFFERENTIATION FACTOR (EDF) ISOLATED FROM HUMAN-LEUKEMIA CELL-LINE THP-1 [J].
ETO, Y ;
TSUJI, T ;
TAKEZAWA, M ;
TAKANO, S ;
YOKOGAWA, Y ;
SHIBAI, H .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1987, 142 (03) :1095-1103
[8]   ACTIVIN-A, INHIBIN AND TRANSFORMING GROWTH FACTOR-BETA MODULATE GROWTH OF 2 GONADAL CELL-LINES [J].
GONZALEZMANCHON, C ;
VALE, W .
ENDOCRINOLOGY, 1989, 125 (03) :1666-1672
[9]  
GREEN JBA, 1990, NATURE, V347, P391, DOI 10.1038/347391a0
[10]  
HASHIMOTO O, 1998, IN PRESS CELL SIGNAL