The novel function of JADE1S in cytokinesis of epithelial cells

Abstract

JADE1 belongs to a small family of PHD zinc finger proteins that interacts with histone acetyl transferase (HAT) HBO1 and is associated with chromatin. We recently reported JADE1 chromatin shuttling and phosphorylation during G2/M to G1 transition, which was sensitive to Aurora A inhibition. In the current study we examined mechanisms of the cell cycle regulation by the small isoform of JADE1 protein, JADE1S, and report data showing that JADE1S has a novel function in the regulation of cytokinesis. Using FACS assays, we show that, JADE1S depletion facilitated rates of G1-cells accumulation in synchronously dividing HeLa cell cultures. Depletion of JADE1S protein in asynchronously dividing cells decreased the proportion of cytokinetic cells, and increased the proportion of multi-nuclear cells, indicative of premature and failed cytokinesis. In contrast, moderate overexpression of JADE1S increased the number of cytokinetic cells in time-and dose-dependent manner, indicating cytokinetic delay. Pharmacological inhibition of Aurora B kinase resulted in the release of JADE1S-mediated cytokinetic delay and allowed progression of abscission in cells overexpressing JADE1S. Finally, we show that JADE1S protein localized to centrosomes in interphase and mitotic cells, while during cytokinesis JADE1S localized to the midbody. Neither JADE1L nor partner of JADE1, HAT HBO1 was localized to the centrosomes or midbodies. Our study identifies the novel role for JADE1S in regulation of cytokinesis and suggests function in Aurora B kinase-mediated cytokinesis checkpoint.

Jade-1S phosphorylation induced by CK1α contributes to cell cycle progression

“…It was recently shown that Jade-1S depletion facilitated the rate of progression through mitosis to G1 in synchronised cells, but that overexpression delayed cytokinesis. 34 Our data supports a model whereby Jade-1S acts to restrain cell cycle rate, and suggests additional roles of Jade-1S throughout the cell cycle. Lowlevel over-expression of both Jade-1S versions enhanced the percentage of cells in G1/G0, and proliferation data supports a mild inhibition of cell cycle rate for these polyclonal lines; however, G2/M:S ratios suggest that every Jade1S.GFP expressing cell that enters S-phase progresses to G2/M, whereas only half of those expressing Jade-1S S18/20A.GFP do.…”

Cut or NoCut: the role of JADE1S in regulating abscission checkpoint

“…Finally, the authors show that Aurora B activity is also required for JADE1S repression of abscission. 6 All data are consistent with JADE1S playing a role in mediating NoCut checkpoint function. JADE1S has emerged as a surprising component of the NoCut checkpoint.…”

“…6 Indeed, HBO1 does not localize to the abscission site and HBO depletion does not appear to affect abscission. Thus, regulation of the NoCut checkpoint appears to be a completely novel function of JADE1.…”

“…In this paper Maria Panachenko and colleagues identified JADE1S as novel regulator of the NoCut checkpoint. 6 Just like ANCHR, JADE1S appears to be a negative regulator of abscission. Consistent with this hypothesis, JADE1S overexpression arrests cells in cytokinesis, while JADE1S depletion leads to a decrease in cytokinesis frequency, presumably due to faster cytokinesis.…”

Structure, function and regulation of jade family PHD finger 1 (JADE1)

“…Importantly, JADE1 is required for the acetylation of bulk histone H4 in cultured cells 22, 23, 25 . In search of the cellular function of JADE1, studies were initiated to examine the JADE1 role in cell cycle progression 5, 6, 23 . While these studies established JADE1 function in cell cycle regulation, the mechanisms of action, the stages involved and, most importantly, the specific contribution of JADE1L and JADE1S isoforms are yet to be identified.…”