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Pregled bibliografske jedinice broj: 1206748

Reciprocal regulation of p21 and Chk1 controls the cyclin D1-RB pathway to mediate senescence onset after G2 arrest


Lossaint Gérald, Horvat Anđela, Gire Véronique, Bačević Katarina, Mrouj Karim, Charrier-Savournin Fabienne, Georget Virginie, Fisher Dan, Dulić Vjekoslav
Reciprocal regulation of p21 and Chk1 controls the cyclin D1-RB pathway to mediate senescence onset after G2 arrest // Journal of cell science, 135 (2022), 8; cs259114, 15 doi:10.1242/jcs.259114 (međunarodna recenzija, članak, znanstveni)


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Naslov
Reciprocal regulation of p21 and Chk1 controls the cyclin D1-RB pathway to mediate senescence onset after G2 arrest

Autori
Lossaint Gérald, Horvat Anđela, Gire Véronique, Bačević Katarina, Mrouj Karim, Charrier-Savournin Fabienne, Georget Virginie, Fisher Dan, Dulić Vjekoslav

Izvornik
Journal of cell science (0021-9533) 135 (2022), 8; Cs259114, 15

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
CDK6 ; Chk1 ; Cyclin D ; DNA damage ; G2 arrest ; RB ; Senescence ; p21

Sažetak
Senescence is an irreversible withdrawal from cell proliferation that can be initiated after DNA damage-induced cell cycle arrest in G2 phase to prevent genomic instability. Senescence onset in G2 requires p53 (also known as TP53) and retinoblastoma protein (RB, also known as RB1) family tumour suppressors, but how they are regulated to convert a temporary cell cycle arrest into a permanent one remains unknown. Here, we show that a previously unrecognised balance between the cyclin-dependent kinase (CDK) inhibitor p21 and the checkpoint kinase Chk1 controls cyclin D-CDK activity during G2 arrest. In non-transformed cells, p21 activates RB in G2 by inhibiting cyclin D1 complexed with CDK2 or CDK4. The resulting G2 exit, which precedes the appearance of senescence markers, is associated with a mitotic bypass, Chk1 downregulation and reduction in the number of DNA damage foci. In p53/RB-proficient cancer cells, a compromised G2 exit correlates with sustained Chk1 activity, delayed p21 induction, untimely cyclin E1 re- expression and genome reduplication. Conversely, Chk1 depletion promotes senescence by inducing p21 binding to cyclin D1- and cyclin E1-CDK complexes and downregulating CDK6, whereas knockdown of the checkpoint kinase Chk2 enables RB phosphorylation and delays G2 exit. In conclusion, p21 and Chk2 oppose Chk1 to maintain RB activity, thus promoting the onset of senescence induced by DNA damage in G2.

Izvorni jezik
Engleski

Znanstvena područja
Biologija



POVEZANOST RADA


Ustanove:
Institut "Ruđer Bošković", Zagreb

Profili:

Avatar Url Anđela Horvat (autor)

Poveznice na cjeloviti tekst rada:

doi journals.biologists.com doi.org

Citiraj ovu publikaciju:

Lossaint Gérald, Horvat Anđela, Gire Véronique, Bačević Katarina, Mrouj Karim, Charrier-Savournin Fabienne, Georget Virginie, Fisher Dan, Dulić Vjekoslav
Reciprocal regulation of p21 and Chk1 controls the cyclin D1-RB pathway to mediate senescence onset after G2 arrest // Journal of cell science, 135 (2022), 8; cs259114, 15 doi:10.1242/jcs.259114 (međunarodna recenzija, članak, znanstveni)
Lossaint Gérald, Horvat Anđela, Gire Véronique, Bačević Katarina, Mrouj Karim, Charrier-Savournin Fabienne, Georget Virginie, Fisher Dan, Dulić Vjekoslav (2022) Reciprocal regulation of p21 and Chk1 controls the cyclin D1-RB pathway to mediate senescence onset after G2 arrest. Journal of cell science, 135 (8), cs259114, 15 doi:10.1242/jcs.259114.
@article{article, year = {2022}, pages = {15}, DOI = {10.1242/jcs.259114}, chapter = {cs259114}, keywords = {CDK6, Chk1, Cyclin D, DNA damage, G2 arrest, RB, Senescence, p21}, journal = {Journal of cell science}, doi = {10.1242/jcs.259114}, volume = {135}, number = {8}, issn = {0021-9533}, title = {Reciprocal regulation of p21 and Chk1 controls the cyclin D1-RB pathway to mediate senescence onset after G2 arrest}, keyword = {CDK6, Chk1, Cyclin D, DNA damage, G2 arrest, RB, Senescence, p21}, chapternumber = {cs259114} }
@article{article, year = {2022}, pages = {15}, DOI = {10.1242/jcs.259114}, chapter = {cs259114}, keywords = {CDK6, Chk1, Cyclin D, DNA damage, G2 arrest, RB, Senescence, p21}, journal = {Journal of cell science}, doi = {10.1242/jcs.259114}, volume = {135}, number = {8}, issn = {0021-9533}, title = {Reciprocal regulation of p21 and Chk1 controls the cyclin D1-RB pathway to mediate senescence onset after G2 arrest}, keyword = {CDK6, Chk1, Cyclin D, DNA damage, G2 arrest, RB, Senescence, p21}, chapternumber = {cs259114} }

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


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