Parkin induces G2/M cell cycle arrest in TNF-α-treated HeLa cells
Autor: | Yeo Wool Kang, Yoonjung Cho, Min Ho Lee, Sung-Hoon Kim, Ki Jong Rhee, Byung Chul Jung, Yoon Suk Kim, Cheol-Ho Pan |
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Rok vydání: | 2015 |
Předmět: |
Cell cycle checkpoint
Cell Survival Ubiquitin-Protein Ligases Biophysics Biology Biochemistry Parkin CDC2 Protein Kinase Humans Viability assay Cyclin B1 Phosphorylation RNA Small Interfering Molecular Biology Mitosis Cyclin-dependent kinase 1 Tumor Necrosis Factor-alpha Cell Biology Cell cycle Cyclin-Dependent Kinases nervous system diseases Cell biology DNA-Binding Proteins G2 Phase Cell Cycle Checkpoints Gene Expression Regulation Neoplastic Cancer cell HeLa Cells Signal Transduction Transcription Factors |
Zdroj: | Biochemical and Biophysical Research Communications. 464:63-69 |
ISSN: | 0006-291X |
Popis: | Parkin is a known tumor suppressor. However, the mechanism by which parkin acts as a tumor suppressor remains to be fully elucidated. Previously, we reported that parkin expression induces caspase-dependent apoptotic cell death in TNF-α-treated HeLa cells. However, at that time, we did not consider the involvement of parkin in cell cycle control. In the current study, we investigated whether parkin is involved in cell cycle regulation and suppression of cancer cell growth. In our cell cycle analyses, parkin expression induced G2/M cell cycle arrest in TNF-α-treated HeLa cells. To elucidate the mechanism(s) by which parkin induces this G2/M arrest, we analyzed cell cycle regulatory molecules involved in the G2/M transition. Parkin expression induced CDC2 phosphorylation which is known to inhibit CDC2 activity and cause G2/M arrest. Cyclin B1, which is degraded during the mitotic transition, accumulated in response to parkin expression, thereby indicating parkin-induced G2/M arrest. Next, we established that Myt1, which is known to phosphorylate and inhibit CDC2, increased following parkin expression. In addition, we found that parkin also induces increased Myt1 expression, G2/M arrest, and reduced cell viability in TNF-α-treated HCT15 cells. Furthermore, knockdown of parkin expression by parkin-specific siRNA decreased Myt1 expression and phosphorylation of CDC2 and resulted in recovered cell viability. These results suggest that parkin acts as a crucial molecule causing cell cycle arrest in G2/M, thereby suppressing tumor cell growth. |
Databáze: | OpenAIRE |
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