Title: Cdh1, a substrate-recruiting component of anaphase-promoting complex/cyclosome (APC/C) ubiquitin E3 ligase, specifically interacts with phosphatase and tensin homolog (PTEN) and promotes its removal from chromatin.
Authors: Choi, Byeong Hyeok; Pagano, Michele; Huang, Chaunshu; Dai, Wei
Published In J Biol Chem, (2014 Jun 20)
Abstract: A pool of PTEN localizes to the nucleus. However, the exact mechanism by which nuclear PTEN is regulated remains unclear. We have recently reported that Plk1 specifically phosphorylates PTEN on Ser-380 during mitosis. Here we report that PTEN also localized to chromatin and that chromatin PTEN was removed by a proteasome-dependent process during mitotic exit. Pulldown analysis revealed that Cdh1, but not Cdc20, was significantly associated with PTEN. Cdh1 interacted with PTEN via two separate domains, and their interaction was enhanced by MG132, a proteasome inhibitor. Cdh1 negatively controlled the stability of chromatin PTEN by polyubiquitination. Phosphorylation of PTEN on Ser-380 impaired its interaction with Cdh1, thus positively regulating PTEN stability on chromatin. Significantly, the PTEN interaction with Cdh1 was phosphatase-independent, and Cdh1 knockdown via RNAi led to significant accumulation of chromatin PTEN, delaying mitotic exit. Combined, our studies identify Cdh1 as an important regulator of nuclear/chromatin PTEN during mitosis.
PubMed ID: 24811168
MeSH Terms: Anaphase-Promoting Complex-Cyclosome/genetics; Anaphase-Promoting Complex-Cyclosome/metabolism*; Antigens, CD; Cadherins/genetics; Cadherins/metabolism*; Chromatin/genetics; Chromatin/metabolism*; Cysteine Proteinase Inhibitors/pharmacology; Enzyme Stability/drug effects; Enzyme Stability/physiology; HeLa Cells; Humans; Leupeptins/pharmacology; Mitosis/drug effects; Mitosis/physiology*; PTEN Phosphohydrolase/genetics; PTEN Phosphohydrolase/metabolism*; Phosphorylation/drug effects; Phosphorylation/physiology; Ubiquitin-Protein Ligases/genetics; Ubiquitin-Protein Ligases/metabolism*; Ubiquitination/drug effects; Ubiquitination/physiology