DUSP7 Regulates the Activity of ERK2 to Promote Proper Chromosome Alignment During Cell Division

Abstract

SUMMARYHuman cell division is a highly regulated process that relies on the accurate capture and movement of chromosomes to the metaphase plate. Errors in the fidelity of chromosome congression and alignment can lead to improper chromosome segregation, which is correlated with aneuploidy and tumorigenesis. Here we show that the dual specificity phosphatase DUSP7 is important for regulating chromosome alignment. DUSP7 bound to ERK2 and regulated the abundance of active phospho-ERK2 through its phosphatase activity. Overexpression of DUSP7, but not catalytic dead mutants, led to a marked decrease in phopho-ERK2 and mitotic chromosome misalignment, while knockdown of DUSP7 also led to defective chromosome congression that resulted in a prolonged mitosis. Consistently, chemical inhibition of the MEK kinase that phosphorylates ERK2 or ERK2 itself led to chromosome alignment defects. Our results support a model where MEK phosphorylation and DUSP7 dephosphorylation regulate the levels of active phospho-ERK2 to promote proper cell division.

CANVS: an easy-to-use application for the analysis and visualization of mass spectrometry–based protein–protein interaction/association data

“…It's important to note that protein interactions and associations should be validated biochemically. As examples, we recently used the analytical framework included in CANVS to study the PPI/A networks of DUSP7, which helped to define its regulation of ERK2 during mitosis (Guo et al, 2021), and to analyze the PPA networks of core spindle assembly checkpoint proteins (Garcia et al, 2021).…”

“…PPI/As can inform on how a POI is compartmentalized within the cell, how it forms higher-order complexes, how it is regulated, and how it coordinates with other proteins to carry out specific cellular processes in a spatial and temporal manner (Yugandhar et al, 2019;Lu et al, 2020). More broadly PPI/A networks have been used to analyze the composition of cellular structures like centrosomes, kinetochores, cilia, and other organelles, and to define the function of cell cycle proteins (Torres et al, 2011;Firat-Karalar and Stearns, 2015;Cheung et al, 2016;Go et al, 2019;Remnant et al, 2019;Garcia et al, 2021;Guo et al, 2021). Several approaches have been used to identify PPIs including yeast two-hybrid (Fields and Song, 1989;Chien et al, 1991), fluorescent resonance energy transfer (Selvin, 1995), and protein fragment complementation assay (Michnick et al, 2000).…”

LncRNA SNHG16 modulates paclitaxel resistance in breast cancer by regulating Let-7a-5p/DUSP7

“…The accumulated evidences demonstrated that lncRNA including SNHG16 and microRNA could regulate the proliferation, invasion, and chemotherapy sensitivity of cancer cells by binding to miRNA and influencing downstream target gene expression. For example, Shi, et al demonstrated that downregulation the expression of microRNA Let-7a-5p, a kind of tumor suppressors, could inhibit the proliferation, migration and invasion of triple negative breast cancer cells [9]; it is reported that overexpression of DUSP7 in breast cancer could increase the drug resistance of breast cancer cells, and overexpression of Let-7a-5p could promote the sensitivity of breast cancer cells to PTX by targeting down regulation of DUSP7 [10,11,12]. Whether SNHG16 participates in PTX resistance of breast cancer cell line MCF-7 cells and the potential mechanism relationships among SNHG16, Let-7a-5p and DUSP7 in PTX resistance to breast cancer cell line were not very clear.…”