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Mutual protection of ribosomal proteins L5 and L11 from degradation is essential for p53 activation upon ribosomal biogenesis stress


Bursać, Slađana; Cokarić Brdovčak, Maja; Pfannkuchen, Martin; Oršolić, Ines; Golomb, Lior; Zhu, Yan; Katz, Chen; Daftuar, Lylin; Grabušić, Kristina; Vukelić, Iva et al.
Mutual protection of ribosomal proteins L5 and L11 from degradation is essential for p53 activation upon ribosomal biogenesis stress // Proceedings of the National Academy of Sciences of the United States of America, 109 (2012), 50; 20467-20472 doi:10.1073/pnas.1218535109 (međunarodna recenzija, članak, znanstveni)


Naslov
Mutual protection of ribosomal proteins L5 and L11 from degradation is essential for p53 activation upon ribosomal biogenesis stress

Autori
Bursać, Slađana ; Cokarić Brdovčak, Maja ; Pfannkuchen, Martin ; Oršolić, Ines ; Golomb, Lior ; Zhu, Yan ; Katz, Chen ; Daftuar, Lylin ; Grabušić, Kristina ; Vukelić, Iva ; Filić, Vedrana ; Oren, Moshe ; Prives, Carol ; Volarević, Siniša

Izvornik
Proceedings of the National Academy of Sciences of the United States of America (0027-8424) 109 (2012), 50; 20467-20472

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

Ključne riječi
Proteasome; ribosomal stress

Sažetak
Impairment of ribosomal biogenesis can activate the p53protein independently of DNA damage. The ability of ribosomal proteins L5, L11, L23, L26, or S7 to bind Mdm2 and inhibit its ubiquitin ligase activity has been suggested as a critical step in p53 activation under these conditions. Here, we report that L5 and L11 are particularly important for this response. Whereas several other newly synthesized ribosomal proteins are degraded by proteasomes upon inhibition of Pol I activity by actinomycin D, L5 and L11 accumulate in the ribosome-free fraction where they bind to Mdm2. This selective accumulation of free L5 and L11 is due to their mutual protection from proteasomal degradation. Furthermore, the endogenous, newly synthesized L5 and L11 continue to be imported into nucleoli even after nucleolar disruption and colocalize with Mdm2, p53, and promyelocytic leukemia. This suggests that the disrupted nucleoli may provide a platform for L5- and L11- dependent p53 activation, implying a role for the nucleolus in p53 activation by ribosomal biogenesis stress. These findings may have important implications with respect to understanding the pathogenesis of diseases caused by impaired ribosome biogenesis.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti



POVEZANOST RADA


Projekt / tema
062-1081347-0370 - Odgovor stanica sisavaca na pogrešku u sintezi ribozoma in vivo (Siniša Volarević, )

Ustanove
Medicinski fakultet, Rijeka,
Institut "Ruđer Bošković", Zagreb,
Sveučilište u Rijeci - Odjel za informatiku,
Sveučilište u Rijeci - Odjel za biotehnologiju

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
  • EconLit


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