Lee, Min Ho Cho, Yoonjung Jung, Byung Chul Kim, Sung Hoon Kang, Yeo Wool Pan, Cheol-Ho Rhee, Ki-Jong Kim, Yoon Suk 2024-01-20T06:31:18Z 2024-01-20T06:31:18Z 2021-08-31 2015-08-14 0006-291X https://pubs.kist.re.kr/handle/201004/125121 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-alpha-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-alpha-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-alpha-treated HCT15 cells. Furthermore, knockdown of parkin expression by parkin-specific siRNA decreased Mytl 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. (C) 2015 Elsevier Inc. All rights reserved. English ACADEMIC PRESS INC ELSEVIER SCIENCE TUMOR-NECROSIS-FACTOR CANCER GENE OVARIAN PHOSPHORYLATION METABOLISM EXPRESSION RESISTANCE SYNUCLEIN IDENTITY Parkin induces G2/M cell cycle arrest in TNF-alpha-treated HeLa cells Article 10.1016/j.bbrc.2015.05.101 1 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.464, no.1, pp.63 - 69 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 464 1 63 69 scie scopus 000359173200011 2-s2.0-84937636612 Biochemistry & Molecular Biology Biophysics Biochemistry & Molecular Biology Biophysics Article TUMOR-NECROSIS-FACTOR CANCER GENE OVARIAN PHOSPHORYLATION METABOLISM EXPRESSION RESISTANCE SYNUCLEIN IDENTITY Parkin Tumor suppressor Cell cycle CDC2 Myt1