Cloning and functional characterization of Ptpcd2 as a novel cell cycle related protein tyrosine phosphatase that
Doaa H Zineldeen1, Ayman A Wagih, Makoto Nakanishi
1Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Tanta University, Tanta, Egypt. Doaa.eldeen@med.tanta.edu.eg
Abstract:
Faithful transmission of genetic information depends on accurate chromosome segregation as cells exit from mitosis, and errors in chromosomal segregation are catastrophic and may lead to aneuploidy which is the hallmark of cancer. In eukaryotes, an elaborate molecular control system ensures proper orchestration of events at mitotic exit. Phosphorylation of specific tyrosyl residues is a major control mechanism for cellular proliferation and the activities of protein tyrosine kinases and phosphatases must be integrated. Although mitotic kinases are well characterized, phosphatases involved in mitosis remain largely elusive. Here we identify a novel variant of mouse protein tyrosine phosphatase containing domain 1 (Ptpcd1), that we named Ptpcd2. Ptpcd1 is a Cdc14 related centrosomal phosphatase. Our newly identified Ptpcd2 shared a significant homology to yeast Cdc14p (34.1%) and other Cdc14 family of phosphatases. By subcellular fractionation Ptpcd2 was found to be enriched in the cytoplasm and nuclear pellets with catalytic phosphatase activity. By means of immunofluorescence, Ptpcd2 was spatiotemporally regulated in a cell cycle dependent manner with cytoplasmic abundance during mitosis, followed by nuclear localization during interphase. Overexpression of Ptpcd2 induced mitotic exit with decreased levels of some mitotic markers. Moreover, Ptpcd2 failed to colocalize with the centrosomal marker γ-tubulin, suggesting it as a non-centrosomal protein. Taken together, Ptpcd2 phosphatase appears a non-centrosomal variant of Ptpcd1 with probable mitotic functions. The identification of this new phosphatase suggests the existence of an interacting phosphatase network that controls mammalian mitosis and provides new drug targets for anticancer modalities.
Insights
Researchers identified Ptpcd2, a novel phosphatase crucial for accurate chromosome segregation during cell division. This discovery offers new insights into controlling mitosis and potential anticancer drug targets.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Accurate chromosome segregation during mitotic exit is vital for preventing aneuploidy, a hallmark of cancer.
- While mitotic kinases are well-studied, the phosphatases regulating mitosis remain largely unknown.
- Protein tyrosine phosphatases play critical roles in regulating cellular proliferation through phosphorylation control.
Purpose of the Study:
- To identify and characterize novel phosphatases involved in mammalian mitosis.
- To investigate the cellular localization and cell cycle-dependent regulation of the newly identified phosphatase.
- To explore the potential role of the new phosphatase in mitotic exit and its implications for cancer.
Main Methods:
- Identification of a novel mouse protein tyrosine phosphatase variant, Ptpcd2, through homology to Cdc14 family.
- Subcellular fractionation to determine Ptpcd2 enrichment and catalytic activity.
- Immunofluorescence and cell cycle analysis to assess Ptpcd2 spatiotemporal regulation and localization.
- Overexpression studies to evaluate the functional impact of Ptpcd2 on mitotic markers and exit.
Main Results:
- Ptpcd2 exhibits significant homology to yeast Cdc14p and other Cdc14 family phosphatases.
- Ptpcd2 displays catalytic phosphatase activity and is enriched in cytoplasm and nuclear fractions.
- Ptpcd2 is regulated in a cell cycle-dependent manner, localizing to the cytoplasm during mitosis and the nucleus during interphase.
- Overexpression of Ptpcd2 promotes mitotic exit and reduces levels of certain mitotic markers.
- Ptpcd2 does not colocalize with the centrosomal marker γ-tubulin, indicating it is a non-centrosomal protein.
Conclusions:
- Ptpcd2 is a novel, non-centrosomal phosphatase, likely a variant of Ptpcd1, with probable functions in mammalian mitosis.
- The identification of Ptpcd2 suggests a complex phosphatase network controlling mammalian mitosis.
- Ptpcd2 represents a potential new target for anticancer drug development.
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