Chromatin-directed proteomics identifies ZNF84 as a p53-independent regulator of p21 in genotoxic stress response
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 kno...
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| Hauptverfasser: | , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
7 April 2021
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| In: |
Cancers
Year: 2021, Jahrgang: 13, Heft: 9, Pages: 1-24 |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers13092115 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/cancers13092115 Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2072-6694/13/9/2115 
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| Verfasserangaben: | Anna Strzeszewska-Potyrała, Karolina Staniak, Joanna Czarnecka-Herok, Mahmoud-Reza Rafiee, Marcin Herok, Grażyna Mosieniak, Jeroen Krijgsveld and Ewa Sikora |
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| 245 | 1 | 0 | |a Chromatin-directed proteomics identifies ZNF84 as a p53-independent regulator of p21 in genotoxic stress response |c Anna Strzeszewska-Potyrała, Karolina Staniak, Joanna Czarnecka-Herok, Mahmoud-Reza Rafiee, Marcin Herok, Grażyna Mosieniak, Jeroen Krijgsveld and Ewa Sikora |
| 246 | 3 | 3 | |a Chromatin-directed proteomics identifies ZNF eighty-four as a p fifty-three-independent regulator of p twenty-one in genotoxic stress response |
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| 520 | |a 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. | ||
| 650 | 4 | |a <i>CDKN1A</i> | |
| 650 | 4 | |a chemotherapy | |
| 650 | 4 | |a chromatin pulldown | |
| 650 | 4 | |a genotoxic stress | |
| 650 | 4 | |a mass spectrometry | |
| 650 | 4 | |a p21 | |
| 650 | 4 | |a senescence | |
| 650 | 4 | |a ZNF84 | |
| 700 | 1 | |a Staniak, Karolina |e VerfasserIn |4 aut | |
| 700 | 1 | |a Czarnecka-Herok, Joanna |e VerfasserIn |4 aut | |
| 700 | 1 | |a Rafiee, Mahmoud-Reza |e VerfasserIn |4 aut | |
| 700 | 1 | |a Herok, Marcin |e VerfasserIn |4 aut | |
| 700 | 1 | |a Mosieniak, Grażyna |e VerfasserIn |4 aut | |
| 700 | 1 | |a Krijgsveld, Jeroen |e VerfasserIn |0 (DE-588)1163292125 |0 (DE-627)1027502032 |0 (DE-576)507882474 |4 aut | |
| 700 | 1 | |a Sikora, Ewa |e VerfasserIn |4 aut | |
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