Human phosphatase CDC14A regulates actin organization through dephosphorylation of epithelial protein lost in neoplasm

• DOI: 10.1073/pnas.1619356114
• Publication Date: 2017-05-03T00:35:16Z
• Authors: Nan-Peng Chen; Borhan Uddin; Robert Hardt; Wen Ding; Marko Panic; Ilaria Lucibello; Patricia Kammerer; Thomas Ruppert; Elmar Schiebel
• Keywords: Dephosphorylation; Membrane ruffling

CDC14 is an essential dual-specificity phosphatase that counteracts CDK1 activity during anaphase to promote mitotic exit in Saccharomyces cerevisiae Surprisingly, human CDC14A not for cell cycle progression. Instead, it regulates migration and adhesion. Little known about the substrates of hCDC14A counteracting kinases. Here, we combine phospho-proteome profiling proximity-dependent biotin identification identify substrates. Among these targets were actin regulators, including tumor suppressor eplin. EGF-induced rearrangements cytoskeleton by dephosphorylating eplin at two extracellular signal-regulated kinase sites, serine 362 604. hCDC14APD knockout lines exhibited down-regulation E-cadherin a reduction α/β-catenin cell-cell adhesions. Reduction levels mRNA frequently associated with colorectal carcinoma correlated poor prognosis. We therefore propose dephosphorylation reduces dynamics restrict malignancy.