Loss of phosphorylation at tyrosine 211 (Y211) in PCNA (pY211-PCNA) mitigates PCNA function in proliferation, triggers replication fork arrest/collapse, which in turn sets off an anti-tumor inflammatory response, and suppresses distant metastasis.

Nov 19, 2006 · Phosphorylation on Tyr 211 by EGFR stabilizes chromatin-bound PCNA protein and associated functions. Consistently, increased PCNA Tyr 211 phosphorylation coincides with pronounced cell...

Aug 24, 2021 · Our findings suggest that enhanced Y211 phosphorylation of PCNA by the tumor-promoting tyrosine kinases such as EGFR and c-ABL constitutes a pro-tumor mechanism that facilitates evasion from immune surveillance and promotes metastasis.

Jan 10, 2011 · We previously reported that phosphorylation of tyrosine 211 (Y211) on PCNA is important for the proliferative function of PCNA when this protein is associated with the chromatin in cancer cells. Here, we show that the Y211 phosphorylation of PCNA is a frequent event in advanced prostate cancer.

Apr 1, 2014 · Activation of RON stimulated Y211 phosphorylation of PCNA, whereas inhibition of the c-ABL kinase blocked RON-mediated PNCA phosphorylation. Correspondingly, treatment with the Y211F peptide or with imatinib suppressed RON-dependent cell proliferation.

May 5, 2015 · Cells expressing a high level of PCNA-Y211p display significantly reduced fidelity of DNA synthesis because of an elevated rate of nucleotide misincorporation. The results support the conclusion that phosphorylation of PCNA on Y211 inhibits MMR activity and reduces the fidelity of DNA synthesis.

Sep 1, 2024 · PCNA is crucial in DNA replication, playing a pivotal role in the development of complete eukaryotic organisms. The phosphorylation of PCNA at tyrosine 211 (Y211) has been demonstrated to play a significant role in supporting replication forks and, …

Jul 1, 2024 · We explore here how phosphorylation at Y211 affects PCNA recognition of the canonical PIP sequences of the regulatory proteins p21 and p15, which bind with nM and μM affinity, respectively. For that purpose, we have prepared PCNA with p-carboxymethyl-L-phenylalanine (pCMF, a mimetic of phosphorylated tyrosine) at position 211. We have also ...

The phosphorylation of tyrosine114 and 211 (Y114, Y211) stabilizes human PCNA, avoiding its ubiquitination and degradation by the proteasome, or alters PCNA interaction with mismatch repair...

Our findings suggest that enhanced Y211 phosphorylation of PCNA by the tumor-promoting tyrosine kinases such as EGFR and c-ABL constitutes a pro-tumor mechanism that facilitates evasion from immune surveillance and promotes metastasis.