scholarly journals The Cellular Senescence-Inhibited Gene Is Essential for PPM1A Myristoylation To Modulate Transforming Growth Factor β Signaling

2018 ◽  
Vol 38 (23) ◽  
Author(s):  
Feng Zhu ◽  
Nan Xie ◽  
Zhe Jiang ◽  
Guodong Li ◽  
Liwei Ma ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phosphatase Activity ◽  
Cellular Senescence ◽  
Protein Phosphatase ◽  
Transforming Growth Factor ◽  
Regulatory Mechanism ◽  
Biological Significance ◽  
Transforming Growth Factor Β ◽  
Biological Processes ◽  
New Ideas

ABSTRACT The cellular senescence-inhibited gene (CSIG) is implicated in important biological processes, including cellular senescence and apoptosis. Our work showed that CSIG is involved in the myristoylation of the serine/threonine protein phosphatase PPM1A. Previous research has shown that myristoylation is necessary for PPM1A to dephosphorylate Smad2 and Smad3. However, the control and the biological significance of the myristoylation remain poorly understood. In this study, we found that CSIG knockdown disturbs PPM1A myristoylation and reduces the dephosphorylation by PPM1A of its substrate Smad2. By regulating PPM1A myristoylation, CSIG is involved in modulating the signaling of transforming growth factor β (TGF-β). Further study of the mechanism indicated that CSIG facilitates the interaction between N-myristoyltransferase 1 (NMT1) and PPM1A. Taking the data together, we found that CSIG is a regulator of PPM1A myristoylation and TGF-β signaling. By promoting the myristoylation of PPM1A, CSIG enhanced the phosphatase activity of PPM1A and further inhibited TGF-β signaling. This work not only extends the biological significance of CSIG but also provides new ideas and a reference for the study of the regulatory mechanism of myristoylation.

Effects of transforming growth factor-β on normal clonal bone cell populations

1991 ◽  
Vol 69 (2-3) ◽  
pp. 132-140 ◽  
Author(s):  
Rebecca Ber ◽  
Takao Kubota ◽  
Jaro Sodek ◽  
Jane E. Aubin
Keyword(s):  
Alkaline Phosphatase ◽  
Growth Factor ◽  
Phosphatase Activity ◽  
Alkaline Phosphatase Activity ◽  
Transforming Growth Factor ◽  
Bone Cells ◽  
Transforming Growth Factor Β ◽  
Prostaglandin E ◽  
Intracellular Camp ◽  
Type I

Although transforming growth factor-β (TGF-β) has been implicated in the local regulation of bone growth and remodelling, its specific effects on different subpopulations of bone cells have not been elucidated. Cells derived from bone are known to be heterogeneous and include both cells of different lineages and osteoblastic populations with different levels of expression of osteoblast-associated properties. Consequently, we have isolated clonal populations of bone cells to examine more precisely the effects of TGF-β on individual subpopulations. Several clonal populations were isolated by limiting dilution from cells derived from 21-day-old fetal rat calvaria. Two of these clones, RCA 11 and RCB 2, were used here. While the two clones responded similarly to parathyroid hormone (PTH) and isoproterenol (ISP) with increases in intracellular cAMP, prostaglandin E2 (PGE2) elicited a 10-fold higher response in RCB 2 cells compared with RCA 11. RCB 2 cells expressed a 10-fold higher alkaline phosphatase activity compared with RCA 11. Both clones synthesized a variety of bone matrix associated proteins, but only RCA 11 synthesized SPP-1 (osteopontin) constitutively. TGF-β stimulated growth of RCB 2 cells after 24 and 48 h of treatment, but had no effect on growth of RCA 11. TGF-β supported anchorage-independent growth of RCB 2 cells, but not that of RCA 11. A 24-h exposure to TGF-β decreased cAMP responsiveness to PTH and ISP slightly in both clones, but had no effect on PGE2 responses. Significant reductions in alkaline phosphatase activity were seen in both clones after 24- and 48-h treatments with TGF-β. Total protein synthesis as measured by [35S]methionine incorporation was stimulated significantly in both clones, but TGF-β selectively stimulated type I collagen compared with type III collagen. SPARC (osteonectin) and secreted phosphoprotein 1 (SPP-1; osteopontin) were stimulated by TGF-β in both RCA 11 and RCB 2 cells. These results indicate that individual clonal populations of cells within bone may be modulated differentially by TGF-β.Key words: transforming growth factor-β, osteoblasts, clonal cell lines, matrix synthesis.

scholarly journals The effect of interleukin-10 and transforming growth factor β-1 on HLA-DR expression in colonic epithelial cells

1998 ◽  
Vol 7 (1) ◽  
pp. 7-11 ◽  
Author(s):  
M. J. Zimmerman ◽  
G. R. Radford-Smith ◽  
D. P. Jewell
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Transforming Growth Factor ◽  
Flow Cytometric Analysis ◽  
Biological Significance ◽  
Transforming Growth Factor Β ◽  
Interleukin 10 ◽  
Colonic Epithelial Cells ◽  
Hla Dr ◽  
Dose Dependent Fashion

The aim of this study was to assess whether interleukin-10 (IL-10) and/or transforming growth factor β-1 (TGF β1) downregulate HLA-DR expression using the HT29 cell line as a model of colonic epithelial cells. HLA-DR expression was induced in HT29 cells withγ-interferon. The effects of IL-10 alone, TGF β1alone, and IL-10 and TGF β1in combination were studied. HLA-DR expression was assessed using flow cytometric analysis.γ-Interferon induced HLA-DR expression in a dose-dependent fashion. In the absence ofγ-interferon, neither IL-10 nor TGF β1induced HLA-DR expression. In isolation, neither IL10 nor TGF β1downregulated HLA-DR expression. When IL-10 and TGF β1were added in combination, small (6-30%) statistically significant reductions in HLA-DR expression were seen. The biological significance is unclear.

scholarly journals Protein phosphatase 5 modulates SMAD3 function in the transforming growth factor‐β pathway

2012 ◽  
Vol 24 (11) ◽  
pp. 1999-2006 ◽  
Author(s):  
David L. Bruce ◽  
Thomas Macartney ◽  
Weidong Yong ◽  
Weinian Shou ◽  
Gopal P. Sapkota
Keyword(s):  
Growth Factor ◽  
Protein Phosphatase ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Protein Phosphatase 5
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