Characteristics of the intron involvement in the mitogen-induced expression of Zfp-36.

The Journal of Biological Chemistry
W S LaiPerry J Blackshear

Abstract

Zfp-36, the gene encoding the putative zinc finger protein tristetraprolin (TTP), is rapidly induced in fibroblasts by a variety of growth factors. Recent gene knockout experiments have shown that TTP-deficient mice developed arthritis, cachexia, and autoimmunity, all apparently mediated by an excess of tumor necrosis factor alpha. We recently showed that full serum inducibility of Zfp-36 requires elements in the promoter; in addition, removal of the single intron strikingly inhibited serum-induced TTP expression. We show here that replacement of the intron with unrelated sequences, or removal of 95% of the intron but retention of the splice sites, each resulted in the maintenance of approximately 45 and 19%, respectively, of full serum-induced expression. In addition, deletion of intron sequences base pairs 601-655 decreased the serum-induced expression of TTP by 65%. Sequence base pairs 618-626 bound specifically to the transcription factor Sp1; mutation of this binding motif decreased TTP expression by 70%, suggesting that Sp1 binding to this motif contributes to serum induction of Zfp-36. We conclude that full serum-induced expression of Zfp-36 depends on the activation of conventional promoter elements as well as elements ...Continue Reading

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Citations

Feb 4, 2009·Molecular and Cellular Biology·Thierry J HornerPerry J Blackshear
Sep 17, 2010·BMC Cell Biology·Pamela S David GerechtJ David Port
Mar 22, 2012·BMC Molecular Biology·Magdalena FlorkowskaAneta Kasza
Nov 13, 2004·Arthritis Research & Therapy·Danielle M CarrickPerry J Blackshear
Dec 29, 2011·Frontiers in Bioscience (Landmark Edition)·Sandhya SandujaDan A Dixon
Oct 30, 2007·Life Sciences·Ulla JalonenEeva Moilanen
Feb 10, 2007·The FEBS Journal·Nien-Yi LinChing-Jin Chang
Feb 1, 2011·Wiley Interdisciplinary Reviews. RNA·Sandhya SandujaDan A Dixon
Oct 4, 2012·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Noora HuotariRiku Korhonen
Feb 16, 2005·Biochemical Pharmacology·Ulla JalonenEeva Moilanen
May 26, 2004·Biochemical and Biophysical Research Communications·Patrícia A MörkingStenio P Fragoso
Nov 19, 2011·Biochimica Et Biophysica Acta·Brian C GeyerHermona Soreq
Nov 28, 2002·Journal of Applied Microbiology·H J OakeyL Owens
Nov 28, 2014·Molecular Pharmacology·Pavan Prabhala, Alaina J Ammit
Jan 18, 2002·The Journal of Biological Chemistry·Ruth S PhillipsPerry J Blackshear
Oct 25, 2014·The Journal of Biological Chemistry·Youn-Jeong ChoiPerry J Blackshear
Dec 6, 2012·Molecular Biology Reports·Yu-Ling ChenChing-Jin Chang
May 26, 2021·Proceedings of the National Academy of Sciences of the United States of America·Guangyin XiJianhui Tian
May 23, 2007·Archives of Biochemistry and Biophysics·Danielle M Carrick, Perry J Blackshear

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