Table 1 The regulatory mechanism of PTEN activity

Transcriptional regulation

protein-protein interaction

RBM24 directly binds and stabilizes PTEN mRNA

Silencing of YTHDC1 decreases PTEN expression and destabilizes PTEN mRNAs

[59]

[60]

IncRNA

lncRNA UFC1 binds to EZH2 and mediates its aggregation in the promoter region of the PTEN gene, epigenetically silencing PTEN expression

[61]

miRNA targeting

miR-26a-5p targeting the 5′UTR of PTEN promotes cell proliferation and G1/S transition in RA-FLS

[64]

miR-214 activates the AKT signaling pathway by directly targeting PTEN and MIR31HG

[65]

miR-3-1p promotes IL-1β-induced chondrocyte pyroptosis by inhibiting PTEN expression

[66]

miR-10b promotes RA progression by targeting PTEN to disrupt the balance between CD4 T cell subsets

[67]

Post-translational

modifier

ubiquitination

HRD1, STX3, and GFPT1 promote ubiquitination degradation of PTEN, which promotes cancer cell proliferation in vivo

[69,70,71]

The ubiquitination of PTEN at lysine position 13 regulates its nuclear localization and suppresses DNA damage in vivo

[73]

Ubiquitination at lysine 221 leads to degradation of PTEN and indirectly impairs HR leading to instability of DSB

[74]

phosphorylation

The enhancement of DNA repair processes, mediating resistance to DNA damage, is facilitated by the phosphorylation of PTEN at tyrosine 240

[75]

Phosphorylation of PTEN serine 113 associated with PTEN nuclear translocation and autophagy

[76]

The proper activation of the S-phase checkpoint, regulated by PI3K-p27, is contingent upon the phosphorylation of PTEN at position 398

[77]

acetylation

The interaction of PTEN with proteins containing PDZ structural domains can potentially be regulated by the acetylation of PTEN at the lysine 402 position

[78]

methylation

PTEN methylation promotes FLS inflammation and activation

[83]

PTEN hypermethylation promotes angiogenesis in experimental arthritis

[84]