PRR16

PRR16 (Largen) is a regulator of mammalian cell size that acts post-transcriptionally by preferentially stimulating translation of specific mRNA subsets, including those encoding mitochondrial proteins, thereby increasing mitochondrial mass and ATP production to drive cell enlargement independently of mTOR signaling (PMID:24656129). This growth-promoting activity was confirmed in vivo, where conditional transgenic overexpression increased cell size (PMID:24656129). In a distinct activity, PRR16 binds directly to ABI2 and interferes with ABI2-mediated inhibition of ABL1 kinase, increasing ABL1 Y412 phosphorylation and promoting epithelial-mesenchymal transition, migration, and invasion in breast cancer cells (PMID:35719027). Beyond these translational and ABL1-axis roles, no further mechanistic detail has been characterized in the available corpus.

1. 2014 High

   Established that PRR16 controls cell size through a defined molecular route — preferential translation of mitochondrial mRNAs — rather than through canonical mTOR growth signaling.

   Evidence Genetic screen for cell-size genes, in vitro translation assays, mitochondrial mass/ATP measurements, and a conditional transgenic mouse model

   PMID:24656129

   Open questions at the time

   • Molecular mechanism by which PRR16 selects specific mRNAs for translation is not defined
   • No structural or biochemical characterization of how PRR16 engages the translation machinery
   • Direct binding partners mediating the translational selectivity are unidentified
2. 2022 Medium

   Identified a separate, growth-independent function whereby PRR16 activates ABL1 kinase by sequestering its inhibitor ABI2, linking PRR16 to EMT and invasion in cancer.

   Evidence Binding partner screen (Co-IP/pulldown), ABI2 silencing and overexpression, ABL1 Y412 phosphoblotting, and migration/invasion assays in MCF7 cells

   PMID:35719027

   Open questions at the time

   • Single-lab finding; mapping of the PRR16–ABI2 interaction interface not determined
   • Relationship between the cell-size/translation role and the ABL1 axis is unresolved
   • In vivo relevance of the ABL1 activation to tumor progression not tested
3. 2008 Low

   Correlated PRR16 expression with a venous/progenitor endothelial phenotype, the earliest observation linking the gene to cell state.

   Evidence Gene expression profiling of arterial vs venous fetal placental endothelial cells with adipogenic/osteogenic differentiation assays

   PMID:18673379

   Open questions at the time

   • Correlative only — no direct manipulation of PRR16 to establish causality
   • No mechanistic link to the translational or ABL1 functions
   • Single lab, no functional follow-up

• How PRR16's translational selectivity, ABL1 activation, and endothelial-state association mechanistically interconnect remains unknown.
• No unifying molecular mechanism linking the two characterized activities
• No structural data on PRR16 or its functional domains
• Direct RNA or protein binding determinants undefined