Table 1.
ARF roles in cell proliferation and molecular mechanisms of the observed function.
| Functions | Mechanisms |
|---|---|
| Tumor Suppression | |
| Growth control | p53 dependent and independent call cycle arrest and apoptosis. ΔNp63 inhibition [4,5,11,12,13,31,32,33,34,42,43,55,79,80] |
| Chromosomal stability | Stabilization of miotic spindle, prevents aneuploidy [62] |
| Ribosomal biogenesis | Inhibition or rRNA processing and transcription [84,85,86,87] |
| Oxidative stress | Cellular protection from dysfunctional mitochondria [61] |
| DNA damage | Activation of ATM/ATR/CHK pathway, p53-dependent pathways of DNA repair [115,116] |
| Contest Dependent | |
| Autophagy | Beclin-1 activation, dissipation of mitochondrion potential [60,123,124,125,126,127] |
| Differentiation | Inhibits angiogenesis in developing eye, protects from apoptosis in spermatogonia, allows extraembryonic endoderm migration [79,110,111,112,113,114,115,116,117] |
| Tumor Promoter | |
| Epithelial to mesechimal transition | Slug stabilization [139] |
| Modulation of tumor microenvironment | Metallopeptidase-1 interaction [141] |
| Survival of lymphoma, protease and bladder tumor cells | Promotes prostate cancer in Pten mouse model and autophagy in lymphomas; promotes chemoresistance in bladder cancer [120,121,122,123,124,125,126,127,138,141,147] |
| Anoikis protection, increased proliferation | Inhibition of DAPK mediated cell death; activation focal adhesion kinase [67,160,161,162] |