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The novel mouse Polo-like kinase 5 responds to DNA damage and localizes in the nucleolus.

Andrysik Z, Bernstein WZ, Deng L, Myer DL, Li YQ, Tischfield JA, Stambrook PJ, Bahassi el M - Nucleic Acids Res. (2010)

Bottom Line: Here, we report the cloning of a fifth member of the polo-like kinase family named Plk5.DNA and protein sequence analyses show that Plk5 shares more similarities with Plk2 and Plk3 than with Plk1 and Plk4.Ectopic expression of Plk5 leads to cell cycle arrest in G1, decreased DNA synthesis, and to apoptosis, a characteristic it shares with Plk3.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.

ABSTRACT
Polo-like kinases (Plk1-4) are emerging as an important class of proteins involved in many aspects of cell cycle regulation and response to DNA damage. Here, we report the cloning of a fifth member of the polo-like kinase family named Plk5. DNA and protein sequence analyses show that Plk5 shares more similarities with Plk2 and Plk3 than with Plk1 and Plk4. Consistent with this observation, we show that mouse Plk5 is a DNA damage inducible gene. Mouse Plk5 protein localizes predominantly to the nucleolus, and deletion of a putative nucleolus localization signal (NoLS) within its N-terminal moiety disrupts its nucleolar localization. Ectopic expression of Plk5 leads to cell cycle arrest in G1, decreased DNA synthesis, and to apoptosis, a characteristic it shares with Plk3. Interestingly, in contrast to mouse Plk5 gene, the sequence of human Plk5 contains a stop codon that produces a truncated protein lacking part of the kinase domain.

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Plk5 expression is induced following different stress stimuli. (A) Murine NIH 3T3 cells were either left untreated (control) or treated for 18 h with the DNA damaging agents etoposide (Etop) or HU, the spindle disassembly agent, nocodazole (Noc) or were serum starved (SS). (B) Human HEK293 cells were either left untreated (control) or treated with DNA damaging agent etoposide or doxorubicin for 6 or 24 h. The Plk5 mRNA level was measured by qPCR in both cases.
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Figure 5: Plk5 expression is induced following different stress stimuli. (A) Murine NIH 3T3 cells were either left untreated (control) or treated for 18 h with the DNA damaging agents etoposide (Etop) or HU, the spindle disassembly agent, nocodazole (Noc) or were serum starved (SS). (B) Human HEK293 cells were either left untreated (control) or treated with DNA damaging agent etoposide or doxorubicin for 6 or 24 h. The Plk5 mRNA level was measured by qPCR in both cases.

Mentions: Plk5 has more characteristics in common with Plk2 and Plk3 than with Plk1 and Plk4. We therefore asked whether expression of Plk5 like Plk2 and Plk3, is inducible by DNA damage. Murine NIH3T3 cells were treated with DNA damaging agents and the levels of Plk5 mRNA transcript were assessed by qPCR. The levels of Plk5 mRNA increased markedly following DNA damage by treatment with etoposide, a topoisomerase II inhibitor that induces DNA double strand breaks (Figure 5A and B). Nocodazole, which interferes with microtubule polymerization and activates the spindle checkpoint, also induced Plk5 expression, as did inhibition of replication by HU. Interestingly, serum starvation also elevated levels of Plk5 mRNA (Figure 5A), but this increase was reversed upon addition of serum (data not shown). This finding distinguishes Plk5 from Plk3 which is serum inducible. The broad range of reagents that can induce Plk5 expression indicates that Plk5 is a stress inducible gene with potential involvement in a variety of processes designed to protect cells from a wide range of insults.Figure 5.


The novel mouse Polo-like kinase 5 responds to DNA damage and localizes in the nucleolus.

Andrysik Z, Bernstein WZ, Deng L, Myer DL, Li YQ, Tischfield JA, Stambrook PJ, Bahassi el M - Nucleic Acids Res. (2010)

Plk5 expression is induced following different stress stimuli. (A) Murine NIH 3T3 cells were either left untreated (control) or treated for 18 h with the DNA damaging agents etoposide (Etop) or HU, the spindle disassembly agent, nocodazole (Noc) or were serum starved (SS). (B) Human HEK293 cells were either left untreated (control) or treated with DNA damaging agent etoposide or doxorubicin for 6 or 24 h. The Plk5 mRNA level was measured by qPCR in both cases.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2875007&req=5

Figure 5: Plk5 expression is induced following different stress stimuli. (A) Murine NIH 3T3 cells were either left untreated (control) or treated for 18 h with the DNA damaging agents etoposide (Etop) or HU, the spindle disassembly agent, nocodazole (Noc) or were serum starved (SS). (B) Human HEK293 cells were either left untreated (control) or treated with DNA damaging agent etoposide or doxorubicin for 6 or 24 h. The Plk5 mRNA level was measured by qPCR in both cases.
Mentions: Plk5 has more characteristics in common with Plk2 and Plk3 than with Plk1 and Plk4. We therefore asked whether expression of Plk5 like Plk2 and Plk3, is inducible by DNA damage. Murine NIH3T3 cells were treated with DNA damaging agents and the levels of Plk5 mRNA transcript were assessed by qPCR. The levels of Plk5 mRNA increased markedly following DNA damage by treatment with etoposide, a topoisomerase II inhibitor that induces DNA double strand breaks (Figure 5A and B). Nocodazole, which interferes with microtubule polymerization and activates the spindle checkpoint, also induced Plk5 expression, as did inhibition of replication by HU. Interestingly, serum starvation also elevated levels of Plk5 mRNA (Figure 5A), but this increase was reversed upon addition of serum (data not shown). This finding distinguishes Plk5 from Plk3 which is serum inducible. The broad range of reagents that can induce Plk5 expression indicates that Plk5 is a stress inducible gene with potential involvement in a variety of processes designed to protect cells from a wide range of insults.Figure 5.

Bottom Line: Here, we report the cloning of a fifth member of the polo-like kinase family named Plk5.DNA and protein sequence analyses show that Plk5 shares more similarities with Plk2 and Plk3 than with Plk1 and Plk4.Ectopic expression of Plk5 leads to cell cycle arrest in G1, decreased DNA synthesis, and to apoptosis, a characteristic it shares with Plk3.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.

ABSTRACT
Polo-like kinases (Plk1-4) are emerging as an important class of proteins involved in many aspects of cell cycle regulation and response to DNA damage. Here, we report the cloning of a fifth member of the polo-like kinase family named Plk5. DNA and protein sequence analyses show that Plk5 shares more similarities with Plk2 and Plk3 than with Plk1 and Plk4. Consistent with this observation, we show that mouse Plk5 is a DNA damage inducible gene. Mouse Plk5 protein localizes predominantly to the nucleolus, and deletion of a putative nucleolus localization signal (NoLS) within its N-terminal moiety disrupts its nucleolar localization. Ectopic expression of Plk5 leads to cell cycle arrest in G1, decreased DNA synthesis, and to apoptosis, a characteristic it shares with Plk3. Interestingly, in contrast to mouse Plk5 gene, the sequence of human Plk5 contains a stop codon that produces a truncated protein lacking part of the kinase domain.

Show MeSH
Related in: MedlinePlus