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. Preprints2023, 2023091653. https://doi.org/10.20944/preprints202309.1653.v2
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. Preprints 2023, 2023091653. https://doi.org/10.20944/preprints202309.1653.v2
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. Preprints2023, 2023091653. https://doi.org/10.20944/preprints202309.1653.v2
APA Style
Krześniak, M., Łasut-Szyszka, B., Będzińska, A., Gdowicz-Kłosok, A., & Rusin, M. (2024). The p53 tumor suppressor protein activates transcription of DUSP13 isoform from the alternative promoter in intron. Preprints. https://doi.org/10.20944/preprints202309.1653.v2
Chicago/Turabian Style
Krześniak, M., Agnieszka Gdowicz-Kłosok and Marek Rusin. 2024 "The p53 tumor suppressor protein activates transcription of DUSP13 isoform from the alternative promoter in intron" Preprints. https://doi.org/10.20944/preprints202309.1653.v2
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 upregulat-ed 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. In cancer cells ex-posed to A+N, DUSP13 is expressed from an alternative promoter in intron, what results in ex-pression of isoform named TMDP-L1. The luciferase reporter tests demonstrated that this pro-moter 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 de-tected 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 or by nutlin-3a acting alone. 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.
