Version 1
: Received: 22 September 2023 / Approved: 25 September 2023 / Online: 25 September 2023 (09:21:39 CEST)
Version 2
: Received: 26 February 2024 / Approved: 26 February 2024 / Online: 26 February 2024 (16:55:16 CET)
How to cite:
Krześniak, M.; Łasut-Szyszka, B.; Będzińska, A.; Gdowicz-Kłosok, A.; Rusin, M. The p53 tumor suppressor protein activates transcription of DUSP13 isoform from the alternative promoter in intron 3. Preprints2023, 2023091653. https://doi.org/10.20944/preprints202309.1653.v1
Krześniak, M.; Łasut-Szyszka, B.; Będzińska, A.; Gdowicz-Kłosok, A.; Rusin, M. The p53 tumor suppressor protein activates transcription of DUSP13 isoform from the alternative promoter in intron 3. Preprints 2023, 2023091653. https://doi.org/10.20944/preprints202309.1653.v1
Krześniak, M.; Łasut-Szyszka, B.; Będzińska, A.; Gdowicz-Kłosok, A.; Rusin, M. The p53 tumor suppressor protein activates transcription of DUSP13 isoform from the alternative promoter in intron 3. Preprints2023, 2023091653. https://doi.org/10.20944/preprints202309.1653.v1
APA Style
Krześniak, M., Łasut-Szyszka, B., Będzińska, A., Gdowicz-Kłosok, A., & Rusin, M. (2023). The p53 tumor suppressor protein activates transcription of DUSP13 isoform from the alternative promoter in intron 3. Preprints. https://doi.org/10.20944/preprints202309.1653.v1
Chicago/Turabian Style
Krześniak, M., Agnieszka Gdowicz-Kłosok and Marek Rusin. 2023 "The p53 tumor suppressor protein activates transcription of DUSP13 isoform from the alternative promoter in intron 3" Preprints. https://doi.org/10.20944/preprints202309.1653.v1
Abstract
The p53 tumor suppressor protein is an activator of transcription. Diverse stress factors lead to various sets of posttranslational modifications of p53 what results in different sets of upregulated genes. We noticed that actinomycin D and nutlin-3a (A+N) synergize in inducing activating phosphorylations of p53 and upregulation of selected p53-target genes. Here we found that one of these genes is DUSP13, which codes for poorly-studied, dual-specificity phosphatase having at least two isoforms, one expressed in testis and the other in skeletal muscles. We found that in cancer cells exposed to A+N, DUSP13 is expressed from an alternative promoter in intron 3, what results in expression of isoform named TMDP-L1. The luciferase reporter tests demonstrated that this promoter is activated by both endogenous and ectopically expressed p53. We showed for the first time that mRNA expressed from this promoter actually produces the protein, which can be detected by Western blotting in all examined cancer cell lines with wild-type p53 exposed to A+N. In some cell lines it is also induced by clinically relevant camptothecin. This isoform, fused with green fluorescent protein localizes in perinuclear region of cells. Thus, TMDP-L1 isoform may be an important element of p53-regulated stress response system.
Keywords
p53; MDM2; DUSP13; alternative promoter; dual-specificity phosphatase
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
