The Dual-Specificity Phosphatase CDC14B Bundles and Stabilizes Microtubules

Abstract

The Cdc14 dual-specificity phosphatases regulate key events in the eukaryotic cell cycle. However, little is known about the function of mammalian CDC14B family members. Here, we demonstrate that subcellular localization of CDC14B protein is cell cycle regulated. CDC14B can bind, bundle, and stabilize microtubules in vitro independently of its catalytic activity. Basic amino acid residues within the nucleolar targeting domain are important for both retaining CDC14B in the nucleolus and preventing microtubule bundling. Overexpression of CDC14B resulted in the formation of cytoplasmic CDC14B and microtubule bundles in interphase cells. These microtubule bundles were resistant to microtubule depolymerization reagents and enriched in acetylated ␣-tubulin. Expression of cytoplasmic forms of CDC14B impaired microtubule nucleation from the microtubule organization center. CDC14B is thus a novel microtubule-bundling and -stabilizing protein, whose regulated subcellular localization may help modulate spindle and microtubule dynamics in mitosis.

Hippo signalling in the G2/M cell cycle phase: Lessons learned from the yeast MEN and SIN pathways

“…However, this does not mean that Cdc14 has no role to play in mitosis, since overexpression of Cdc14 leads to cytokinesis defects in mammalian cells [18]. In addition, Cdc14 can be detected at the spindle midzone and midbody in animal cells [97][98][99][100][101]. These reports suggest that mammalian Cdc14 phosphatases are not essential for mitotic progression, although they can have negative effects on mitotic processes upon overexpression.…”

Nucleophosmin/B23 Negatively Regulates GCN5-dependent Histone Acetylation and Transactivation

“…GST-cyclin E-CDK2 complex was purified with glutathione-agarose beads from Sf9 insect cells coinfected with baculoviruses expressing cyclin E and CDK2. GST-GCN5 and B23-His fusions were purified from Escherichia coli in essentially the same manner as described previously (28).…”

The Cdc14B phosphatase displays oncogenic activity mediated by the Ras-Mek signaling pathway

“…29,33 Overexpression of Cdc14B has been previously described to result in microtubules bundling and stabilization as well as decreased microtubule nucleation from the centrosome. 22 Thus, it is possible that some of the effects in cell movements may be due to a direct role of Cdc14B on microtubule dynamics. However, these effects seem to be independent of the phosphatase activity of Cdc14B, 22 and it ©2 0 1 1 L a n d e s B i o s c i e n c e .…”

“…22 Thus, it is possible that some of the effects in cell movements may be due to a direct role of Cdc14B on microtubule dynamics. However, these effects seem to be independent of the phosphatase activity of Cdc14B, 22 and it ©2 0 1 1 L a n d e s B i o s c i e n c e .…”

“…21 It has also been shown that Cdc14B can bind and stabilize microtubules, leading to an accumulation of acetylated tubulin in microtubule bundles. 22 One of the few described substrates of Cdc14B is the tubulin deacetylase Sirt2, 23,24 thus suggesting a possible indirect involvement of Cdc14B in tubulin Cdc14 is a dual-specific phosphatase with relevant functions during mitotic exit in yeast. the relevance of vertebrate Cdc14 phosphatases is not well understood due to the presence of two paralogs, Cdc14A and Cdc14B, and their dispensability for cell cycle progression.…”