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. 2021 Aug 13;40(41):5975–5983. doi: 10.1038/s41388-021-01991-3

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — 1. The XAF-1 protein binds to the p53 protein in the proline domain and dissociates MDM-2 from p53, stabilizing p53. 2. The XAF-1 protein binds to the ubiquitin ligase SIAH-2, which inhibits its functions, increasing the levels and activity of HIPK-2, which in turn phosphorylates p53-serine 46, which promotes the transcription of a pro-apoptotic p53 pathway. 3. The XAF-1 protein also binds to ZNF-313, a ubiquitin ligase that promotes the degradation of the p21 protein (cell cycle arrest). This is also is a pro-apoptotic activity [46].