S1219 residue of 53BP1 is phosphorylated by ATM kinase upon DNA damage and required for proper execution of DNA damage response |
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Authors: | Lee Haemi Kwak Hee-Jin Cho Il-taeg Park Seok Hee Lee Chang-Hun |
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Affiliation: | INSERM U.542, Université Paris-Sud 11, Hôpital Paul Brousse, 14 Avenue Paul Vaillant Couturier, 94807 Villejuif Cedex, France |
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Abstract: | B lymphocyte receptor-mediated apoptosis is associated with increased expression of the BimL isoform of Bim. The mechanisms involved in the regulation of BimL protein expression are still unknown. We report that BimL expression following BCR activation is not associated with a specific increase of BimL mRNA but rather to the intron retention structure of the BimEL mRNA. Indeed, expression of a BimEL cDNA leads in Hela cells leads to the production of both BimEL and BimL proteins. Mutation of the intron-splicing GT sequence present in the exon 3 results in the production of only BimEL protein. Ectopic expression of BimEL cDNA resulted in a large increase of BimL expression upon BCR-stimulation, whereas cells transfected with the GT/AA mutated form of BimEL only produced BimEL proteins upon BCR-activation. These data showed that BimL expression induced by BCR activation may result from the splicing of BimEL mRNA independently of Bim promoter regulation. |
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Keywords: | Apoptosis Bim Isoforms Intron retention |
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