A C-terminal cytoplasmic retention motif and nuclear localization signal regulates nuclear import of TP53INP2.

ABSTRACT: Tumor protein p53 inducible nuclear protein 2 (TP53INP2; also known as DOR) is a multifunctional protein involved in transcriptional coactivation, ribosomal RNA synthesis and autophagy, regulated by subcellular localization. Using CRISPR/Cas9-generated TP53INP2-knockout HeLa cells reconstituted with EGFP-TP53INP2, we show that TP53INP2 is predominantly degraded by nuclear proteasomes under basal conditions. Under stress, including starvation and various chemical stress inducers, TP53INP2 accumulates in the cytoplasm independently of ATG5, CRM1-mediated export, phosphorylation, ubiquitylation or acetylation. We identify a nuclear localization signal (NLS) overlapping a nucleolar localization signal (NoLS) in the C-terminus, which mediates nuclear import and nucleolar enrichment. Deletion of

SUBMITTER: Shrestha BK 

PROVIDER: S-EPMC12752491 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature