TGF-beta 1 induces the cyclin-dependent kinase inhibitor p27Kip1 mRNA and protein in murine B cells
- PMID:9551912
TGF-beta 1 induces the cyclin-dependent kinase inhibitor p27Kip1 mRNA and protein in murine B cells
Abstract
TGF-beta1 inhibits the cell cycle progression of many types of cells by arresting them in the G1 phase. This cell cycle arrest has been attributed to the regulatory effects of TGF-beta1 on both the levels and the activities of the G1 cyclins and their kinase partners. The activities of these kinases are negatively regulated by a number of proteins, such as p15INK4b, p21WAF1/Cip1, and p27Kip1, that physically associate with cyclins, cyclin-dependent kinases (Cdk), or cyclin-Cdk complexes. In epithelial cell lines, TGF-beta1 was previously shown to inhibit cell cycle progression through down-regulation of Cdk4 and/or up-regulation of p15INK4b and/or p21WAF1/Cip1. However, TGF-beta1 had little or no effect on the p27Kip1 mRNA and protein levels. In this report, we show that, in contrast to observations in epithelial cell lines, TGF-beta1 increased the p27Kip1 mRNA and protein levels in the murine B cell lines CH31 and WEHI231. This TGF-beta1-mediated induction of p27Kip1 also resulted in an increased association of p27Kip1 with Cdk2 and a decreased Cdk2 kinase activity. In contrast to epithelial cells, however, TGF-beta1 had little or no effect on the Cdk4 and p21WAF1/Cip1 protein levels in these B cells. Finally, although several studies suggested a direct role of p53 in TGF-beta1-mediated cell cycle arrest in epithelial cells, TGF-beta1 inhibited cell cycle progression in CH31 even in the absence of wild-type p53. Taken together, these results suggest that TGF-beta1 induces G1 arrest in B cells primarily through a p53-independent up-regulation of p27Kip1 protein.
Similar articles
- Insensitivity to growth inhibition by TGF-beta1 correlates with a lack of inhibition of the CDK2 activity in prostate carcinoma cells.Cipriano SC, Chen YQ.Cipriano SC, et al.Oncogene. 1998 Sep 24;17(12):1549-56. doi: 10.1038/sj.onc.1202069.Oncogene. 1998.PMID:9794232
- Mechanisms of cell cycle arrest in response to TGF-beta in progestin-dependent and -independent growth of mammary tumors.Salatino M, Labriola L, Schillaci R, Charreau EH, Elizalde PV.Salatino M, et al.Exp Cell Res. 2001 Apr 15;265(1):152-66. doi: 10.1006/excr.2001.5175.Exp Cell Res. 2001.PMID:11281653
- Retinoic acid-mediated growth arrest of EBV-immortalized B lymphocytes is associated with multiple changes in G1 regulatory proteins: p27Kip1 up-regulation is a relevant early event.Zancai P, Cariati R, Rizzo S, Boiocchi M, Dolcetti R.Zancai P, et al.Oncogene. 1998 Oct 8;17(14):1827-36. doi: 10.1038/sj.onc.1202089.Oncogene. 1998.PMID:9778049
- [Molecular mechanisms controlling the cell cycle: fundamental aspects and implications for oncology].Viallard JF, Lacombe F, Belloc F, Pellegrin JL, Reiffers J.Viallard JF, et al.Cancer Radiother. 2001 Apr;5(2):109-29. doi: 10.1016/s1278-3218(01)00087-7.Cancer Radiother. 2001.PMID:11355576Review.French.
- Cyclin-dependent kinase regulation during G1 phase and cell cycle regulation by TGF-beta.Ravitz MJ, Wenner CE.Ravitz MJ, et al.Adv Cancer Res. 1997;71:165-207. doi: 10.1016/s0065-230x(08)60099-8.Adv Cancer Res. 1997.PMID:9111866Review.
Cited by
- Transforming growth factor β1 accelerates and enhances in vitro red blood cell formation from hematopoietic stem cells by stimulating mitophagy.Kuhikar R, Khan N, Philip J, Melinkeri S, Kale V, Limaye L.Kuhikar R, et al.Stem Cell Res Ther. 2020 Feb 19;11(1):71. doi: 10.1186/s13287-020-01603-z.Stem Cell Res Ther. 2020.PMID:32075694Free PMC article.
- Transforming growth factor beta 1 promotes cell cycle exit through the cyclin-dependent kinase inhibitor p21 in the developing cerebral cortex.Siegenthaler JA, Miller MW.Siegenthaler JA, et al.J Neurosci. 2005 Sep 21;25(38):8627-36. doi: 10.1523/JNEUROSCI.1876-05.2005.J Neurosci. 2005.PMID:16177030Free PMC article.
- A global genomic view on LNX siRNA-mediated cell cycle arrest.Zheng D, Gu S, Li Y, Ji C, Xie Y, Mao Y.Zheng D, et al.Mol Biol Rep. 2011 Apr;38(4):2771-83. doi: 10.1007/s11033-010-0422-6. Epub 2010 Nov 21.Mol Biol Rep. 2011.PMID:21104141
- The proximal tubule in the pathophysiology of the diabetic kidney.Vallon V.Vallon V.Am J Physiol Regul Integr Comp Physiol. 2011 May;300(5):R1009-22. doi: 10.1152/ajpregu.00809.2010. Epub 2011 Jan 12.Am J Physiol Regul Integr Comp Physiol. 2011.PMID:21228342Free PMC article.Review.
- Transition of kidney tubule cells to a senescent phenotype in early experimental diabetes.Satriano J, Mansoury H, Deng A, Sharma K, Vallon V, Blantz RC, Thomson SC.Satriano J, et al.Am J Physiol Cell Physiol. 2010 Aug;299(2):C374-80. doi: 10.1152/ajpcell.00096.2010. Epub 2010 May 26.Am J Physiol Cell Physiol. 2010.PMID:20505038Free PMC article.
MeSH terms
Substances
Related information
LinkOut - more resources
Research Materials
Miscellaneous