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 or serum depletion, can be significantly attenuated by knocking down L11, indicating the importance of L11 in mediating these growth inhibitory signals to p53. We show that L11 is not regulated by transcription or protein stability and its level remains relatively constant during serum starvation. However, serum starvation induces translocation of L11 from the nucleolus to the nucleoplasm, where it participates in a complex with HDM2. We propose that the nucleolus acts as a barrier to prevent L11 interacting with HDM2 during normal growth. Growth inhibition, presumably through suppression of rRNA production in the nucleolus, facilitates translocation of L11 to the nucleoplasm, thus activating p53 through inhibiting HDM2.
Bhat
Krishna P
KP
Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Itahana
Koji
K
Jin
Aiwen
A
Zhang
Yanping
Y
D000595:Amino Acid Sequence; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000502:physiology*; D045744:Cell Line, Tumor; D016895:Culture Media, Serum-Free; D006801:Humans; D008969:Molecular Sequence Data; D021381:Protein Transport; D012269:Ribosomal Proteins / Q000378:metabolism / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D016895:Culture Media, Serum-Free; D012269:Ribosomal Proteins; D016159:Tumor Suppressor Protein p53; C027624:ribosomal protein L11