Mycophenolic Acid Activation of p53 Requires Ribosomal Proteins L5 and L11

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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 p53 protein 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 synt...

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Essential role of ribosomal protein L11 in mediating growth inhibition-induced p53 activation.

The ribosomal protein L11 binds to and suppresses the E3 ligase function of HDM2, thus activating p53. Despite being abundant as a component of the 60S large ribosomal subunit, L11 does not induce p53 under normal growth conditions. In search of mechanisms controlling L11-HDM2 interaction, we found that the induction of p53 under growth inhibitory conditions, such as low dose of actinomycin D o...

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Loss of Ribosomal Protein L11 Affects Zebrafish Embryonic Development through a p53-Dependent Apoptotic Response

Ribosome is responsible for protein synthesis in all organisms and ribosomal proteins (RPs) play important roles in the formation of a functional ribosome. L11 was recently shown to regulate p53 activity through a direct binding with MDM2 and abrogating the MDM2-induced p53 degradation in response to ribosomal stress. However, the studies were performed in cell lines and the significance of thi...

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Loss of ribosomal protein L11 blocks stress activation of the Bacillus subtilis transcription factor sigma(B).

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Development of Soft Tissue Sarcomas in Ribosomal Proteins L5 and S24 Heterozygous Mice

Diamond-Blackfan anemia (DBA) is an inherited bone marrow failure syndrome associated with ribosomal protein (RP) gene mutations. Recent studies have also demonstrated an increased risk of cancer predisposition among DBA patients. In this study, we report the formation of soft tissue sarcoma in the Rpl5 and Rps24 heterozygous mice. Our observation suggests that even though one wild-type allele ...

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ژورنال

عنوان ژورنال: Journal of Biological Chemistry

سال: 2008

ISSN: 0021-9258

DOI: 10.1074/jbc.m801387200