PAGE4
Developmental stage
Highly expressed in the earlier stages of fetal development, expression decreases dramatically by the time the pre-pubertal prostate buds are developed (36 weeks).
Function
Intrinsically disordered protein that potentiates the transcriptional activator activity of JUN (PubMed:24263171, PubMed:28289210). Protects cells from stress-induced apoptosis by inhibiting reactive oxygen species (ROS) production and via regulation of the MAPK signaling pathway (PubMed:21357425, PubMed:25374899, PubMed:30658679).
Post-translational modifications
HIPK1-mediated phosphorylation at Thr-51 leads to the compaction of its intrinsically disordered conformation and is critical for its ability to potentiate the transcriptional activator activity of JUN inspite of a reduced interaction with JUN (PubMed:24559171, PubMed:26242913). CLK2-mediated phosphorylation at multiple Ser and Thr residues attenuates its ability to potentiate JUN transcriptional activator activity (PubMed:28289210).
Sequence Similarities
Belongs to the GAGE family.
Tissue Specificity
Expressed at basal lvels in the adult normal prostate gland but is highly up-regulated in the fetal prostate and prostate cancer cells (PubMed:12489849, PubMed:24263171, PubMed:24559171, PubMed:25374899). Preferentially expressed in normal male and female reproductive tissues, testis, fallopian tube, uterus, and placenta, as well as in testicular cancer, uterine cancer, cervical cancer and kidney cancer (PubMed:12489849, PubMed:9724777).
Cellular localization
- Cytoplasm
- Nucleus
- Mitochondrion
- Translocates to mitochondria in response to stress.
Alternative names
GAGEC1, JM27, PAGE4, P antigen family member 4, PAGE-4, G antigen family C member 1, PAGE-1