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

Title
Parkin induces G2/M cell cycle arrest in TNF-a-treated HeLa cells
Authors
Min Ho LeeYoonjung ChoByung Chul JungSung Hoon KimYeo Wool Kang판철호Ki-Jong RheeYoon Suk Kim
Keywords
Parkin; Tumor suppressor; Cell cycle; CDC2; Myt1
Issue Date
2015-08
Publisher
Biochemical and biophysical research communications
Citation
VOL 464, NO 1, 63-69
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.
URI
http://pubs.kist.re.kr/handle/201004/50331
ISSN
0006291X
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KIST Publication > Article
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