Mutual protection of ribosomal proteins L5 and L11 from degradation is essential for p53 activation upon ribosomal biogenesis stress (CROSBI ID 197660)
Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija
Podaci o odgovornosti
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
engleski
Mutual protection of ribosomal proteins L5 and L11 from degradation is essential for p53 activation upon ribosomal biogenesis stress
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.
proteasome ; ribosomal stress
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Podaci o izdanju
109 (50)
2012.
20467-20472
objavljeno
0027-8424
1091-6490
10.1073/pnas.1218535109
Povezanost rada
Kemija, Temeljne medicinske znanosti