| Online-Ressource |
Verfasst von: | Strzeszewska-Potyrała, Anna [VerfasserIn]  |
| Staniak, Karolina [VerfasserIn]  |
| Czarnecka-Herok, Joanna [VerfasserIn]  |
| Rafiee, Mahmoud-Reza [VerfasserIn]  |
| Herok, Marcin [VerfasserIn]  |
| Mosieniak, Grażyna [VerfasserIn]  |
| Krijgsveld, Jeroen [VerfasserIn]  |
| Sikora, Ewa [VerfasserIn]  |
Titel: | Chromatin-directed proteomics identifies ZNF84 as a p53-independent regulator of p21 in genotoxic stress response |
Verf.angabe: | Anna Strzeszewska-Potyrała, Karolina Staniak, Joanna Czarnecka-Herok, Mahmoud-Reza Rafiee, Marcin Herok, Grażyna Mosieniak, Jeroen Krijgsveld and Ewa Sikora |
E-Jahr: | 2021 |
Jahr: | 7 April 2021 |
Umfang: | 24 S. |
Teil: | volume:13 |
| year:2021 |
| number:9 |
| elocationid:2115 |
| pages:1-24 |
| extent:24 |
Fussnoten: | Gesehen am 28.06.2021 |
Titel Quelle: | Enthalten in: Cancers |
Ort Quelle: | Basel : MDPI, 2009 |
Jahr Quelle: | 2021 |
Band/Heft Quelle: | 13(2021), 9, Artikel-ID 2115, Seite 1-24 |
ISSN Quelle: | 2072-6694 |
Abstract: | The p21WAF1/Cip1 protein, encoded by CDKN1A, plays a vital role in senescence, and its transcriptional control by the tumour suppressor p53 is well-established. However, p21 can also be regulated in a p53-independent manner, by mechanisms that still remain less understood. We aimed to expand the knowledge about p53-independent senescence by looking for novel players involved in CDKN1A regulation. We used a chromatin-directed proteomic approach and identified ZNF84 as a novel regulator of p21 in various p53-deficient cell lines treated with cytostatic dose of doxorubicin. Knock-down of ZNF84, an as-yet un-characterized protein, inhibited p21 gene and protein expression in response to doxorubicin, it attenuated senescence and was associated with enhanced proliferation, indicating that ZNF84-deficiency can favor senescence bypass. ZNF84 deficiency was also associated with transcriptomic changes in genes governing various cancer-relevant processes e.g., mitosis. In cells with ZNF84 knock-down we discovered significantly lower level of H2AX Ser139 phosphorylation (γH2AX), which is triggered by DNA double strand breaks. Intriguingly, we observed a reverse correlation between the level of ZNF84 expression and survival rate of colon cancer patients. In conclusion, ZNF84, whose function was previously not recognized, was identified here as a critical p53-independent regulator of senescence, opening possibilities for its targeting in novel therapies of p53-null cancers. |
DOI: | doi:10.3390/cancers13092115 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: https://doi.org/10.3390/cancers13092115 |
| Volltext: https://www.mdpi.com/2072-6694/13/9/2115 |
| DOI: https://doi.org/10.3390/cancers13092115 |
Datenträger: | Online-Ressource |
Sprache: | eng |
Sach-SW: | <i>CDKN1A</i> |
| chemotherapy |
| chromatin pulldown |
| genotoxic stress |
| mass spectrometry |
| p21 |
| senescence |
| ZNF84 |
K10plus-PPN: | 176132134X |
Verknüpfungen: | → Zeitschrift |
Chromatin-directed proteomics identifies ZNF84 as a p53-independent regulator of p21 in genotoxic stress response / Strzeszewska-Potyrała, Anna [VerfasserIn]; 7 April 2021 (Online-Ressource)