title: Parkin induces G2/M cell cycle arrest in TNF-α-treated HeLa cells.
abstract: 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.
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju, Gangwon-do, 220-710, Republic of Korea.
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Lee
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju, Gangwon-do, 220-710, Republic of Korea.
authors.forename: Yoonjung
authors.initials: Y
authors.lastname: Cho
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju, Gangwon-do, 220-710, Republic of Korea.
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Jung
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju, Gangwon-do, 220-710, Republic of Korea.
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju, Gangwon-do, 220-710, Republic of Korea.
authors.forename: Yeo Wool
authors.initials: YW
authors.lastname: Kang
authors.affiliation: Laboratory of Biomodulation, KIST Gangneung Institute of Natural Products, Gangneung, Gangwn-do, 210-340, Republic of Korea.
authors.forename: Cheol-Ho
authors.initials: CH
authors.lastname: Pan
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju, Gangwon-do, 220-710, Republic of Korea.
authors.forename: Ki-Jong
authors.initials: KJ
authors.lastname: Rhee
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju, Gangwon-do, 220-710, Republic of Korea. Electronic address: yoonsukkim@yonsei.ac.kr.
authors.forename: Yoon Suk
authors.initials: YS
authors.lastname: Kim
mesh_terms: D016203:CDC2 Protein Kinase; D002470:Cell Survival / Q000187:drug effects; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: C534699:CCNB1 protein, human; D056744:Cyclin B1; D004268:DNA-Binding Proteins; C078341:MYT1 protein, human; D034741:RNA, Small Interfering; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases
keywords: CDC2; Cell cycle; Myt1; Parkin; Tumor suppressor