Parkin induces G2/M cell cycle arrest in TNF-α-treated HeLa cells

Min Ho Lee, Yoonjung Cho, Byung Chul Jung, Sung Hoon Kim, Yeo Wool Kang, Cheol Ho Pan, Kijong Rhee, Yoon Suk Kim

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number33999
Pages (from-to)63-69
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume464
Issue number1
DOIs
Publication statusPublished - 2015 Jul 20

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G2 Phase Cell Cycle Checkpoints
HeLa Cells
Cells
Cell Cycle Checkpoints
Neoplasms
Cell Survival
Cell Cycle
Phosphorylation
Cyclin B1
Tumors
Cell growth
Growth
Caspases
Small Interfering RNA
Cell Death
Molecules
Cell death

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Lee, M. H., Cho, Y., Jung, B. C., Kim, S. H., Kang, Y. W., Pan, C. H., ... Kim, Y. S. (2015). Parkin induces G2/M cell cycle arrest in TNF-α-treated HeLa cells. Biochemical and Biophysical Research Communications, 464(1), 63-69. [33999]. https://doi.org/10.1016/j.bbrc.2015.05.101
Lee, Min Ho ; Cho, Yoonjung ; Jung, Byung Chul ; Kim, Sung Hoon ; Kang, Yeo Wool ; Pan, Cheol Ho ; Rhee, Kijong ; Kim, Yoon Suk. / Parkin induces G2/M cell cycle arrest in TNF-α-treated HeLa cells. In: Biochemical and Biophysical Research Communications. 2015 ; Vol. 464, No. 1. pp. 63-69.
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Parkin induces G2/M cell cycle arrest in TNF-α-treated HeLa cells. / Lee, Min Ho; Cho, Yoonjung; Jung, Byung Chul; Kim, Sung Hoon; Kang, Yeo Wool; Pan, Cheol Ho; Rhee, Kijong; Kim, Yoon Suk.

In: Biochemical and Biophysical Research Communications, Vol. 464, No. 1, 33999, 20.07.2015, p. 63-69.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Parkin induces G2/M cell cycle arrest in TNF-α-treated HeLa cells

AU - Lee, Min Ho

AU - Cho, Yoonjung

AU - Jung, Byung Chul

AU - Kim, Sung Hoon

AU - Kang, Yeo Wool

AU - Pan, Cheol Ho

AU - Rhee, Kijong

AU - Kim, Yoon Suk

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N2 - 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.

AB - 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.

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DO - 10.1016/j.bbrc.2015.05.101

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