Coordinate regulation of cell growth and differentiation by TGF-beta superfamily and Runx proteins.
Runx proteins regulate various biological processes, including growth and differentiation of hematopoietic cells, lymphocytes, osteoblasts, and gastric epithelial cells. Some of the biological activities of Runx proteins are reminiscent of those of transforming growth factor (TGF)-beta superfamily cytokines. Consistent with this notion, receptor-regulated Smads (R-Smads), signal mediators of the TGF-beta superfamily cytokines, and Runx proteins have been shown to physically interact with each other. R-Smads activated by TGF-beta and Runx proteins cooperatively induce synthesis of IgA in B lymphocytes, and those activated by bone morphogenetic proteins and Runx2 induce osteoblastic differentiation. Moreover, the R-Smad-Runx signaling pathways are regulated by an E3 ubiquitin ligase Smurf1, as well as a signal transducer of interferons, STAT1. Since Runxl and Runx3 are involved in the development of some cancers including acute leukemia and gastric cancer, it will be of interest to examine in detail whether TGF-beta-specific R-Smads and Runx proteins coordinately regulate growth and differentiation of hematopoietic cells and gastric epithelial cells.
Miyazono
Kohei
K
Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. miyazano-ind@umin.ac.jp
Maeda
Shingo
S
Imamura
Takeshi
T
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics* / Q000502:physiology; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D050659:Core Binding Factor Alpha 1 Subunit; D050676:Core Binding Factor Alpha 2 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; D050657:Core Binding Factor alpha Subunits; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism
D050659:Core Binding Factor Alpha 1 Subunit; D050676:Core Binding Factor Alpha 2 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; D050657:Core Binding Factor alpha Subunits; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; C493728:RUNX1 protein, human; C493726:Runx1 protein, mouse; C493729:Runx3 protein, human; C493730:Runx3 protein, mouse; D014157:Transcription Factors; D016212:Transforming Growth Factor beta