PICT-1 helps detect DNA damage and controls cell death through the RPL11-MDM2-p53 pathway

Loss of PICT-1 is associated with p53 accumulation and apoptosis.

• DNA damage alters PICT-1 localization and reduces its protein levels through the proteasome pathway.
• The kinases ATM and DNA-PK interact with PICT-1 in the nucleolus.
• PICT-1 may be phosphorylated by PIKKs at specific sites, S233 and T289, which are critical for its response to UVB-induced damage.
• Mutations at S233 and T289 prevent the increase of PICT-1 phosphorylation following DNA damage.
• Inhibition of ATM alters PICT-1 stability and prevents its degradation.
• Phosphorylation and degradation of PICT-1 promote the release of RPL11, which enhances p53 accumulation and apoptosis.

Simplified