| |  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)
