Downregulation of POLD4 in Calu6 cells results in G1-S blockage through suppression of the Akt-Skp2-p27 pathway

Qinmiao Huang; Motoshi Suzuki; Yiming Zeng; Huaping Zhang; Dongyong Yang; Huihuang Lin

doi:10.1016/j.bmcl.2014.02.033

Downregulation of POLD4 in Calu6 cells results in G1-S blockage through suppression of the Akt-Skp2-p27 pathway

Qinmiao Huang
, Motoshi Suzuki
, Yiming Zeng
, Huaping Zhang
, Dongyong Yang
, Huihuang Lin

研究成果: ジャーナルへの寄稿 › 学術論文 › 査読

7 被引用数 (Scopus)

抄録

Previously, we have shown that downregulation of POLD4 in lung cancer cells delays progression through the G1-S cell cycle transition and leads to increased genomic instability. To date however, detailed molecular mechanisms have not been elucidated to explain how this occurs. In the present study, we found that reduction in POLD4 by siRNA knockdown promoted downregulation of both p-Akt Ser473 and Skp2 as well as upregulation of p27. Furthermore, these protein expression levels were rescued when siRNA-resistant POLD4 was ectopically expressed in the knockdown cells. These data suggest that the POLD4 downregulation is associated with impaired Akt-Skp2-p27 pathway in lung cancer.

本文言語	英語
ページ（範囲）	1780-1783
ページ数	4
ジャーナル	Bioorganic and Medicinal Chemistry Letters
巻	24
号	7
DOI	https://doi.org/10.1016/j.bmcl.2014.02.033
出版ステータス	出版済み - 01-04-2014
外部発表	はい

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All Science Journal Classification (ASJC) codes

生化学
分子医療
分子生物学
薬科学
創薬
臨床生化学
有機化学

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10.1016/j.bmcl.2014.02.033

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title = "Downregulation of POLD4 in Calu6 cells results in G1-S blockage through suppression of the Akt-Skp2-p27 pathway",

abstract = "Previously, we have shown that downregulation of POLD4 in lung cancer cells delays progression through the G1-S cell cycle transition and leads to increased genomic instability. To date however, detailed molecular mechanisms have not been elucidated to explain how this occurs. In the present study, we found that reduction in POLD4 by siRNA knockdown promoted downregulation of both p-Akt Ser473 and Skp2 as well as upregulation of p27. Furthermore, these protein expression levels were rescued when siRNA-resistant POLD4 was ectopically expressed in the knockdown cells. These data suggest that the POLD4 downregulation is associated with impaired Akt-Skp2-p27 pathway in lung cancer.",

author = "Qinmiao Huang and Motoshi Suzuki and Yiming Zeng and Huaping Zhang and Dongyong Yang and Huihuang Lin",

note = "Funding Information: This work was supported by the National Natural Science Foundation of China (Grant No. 81141093 ), the Science Foundation of the Fujian Province, China (Grant No. 2013J01290 ) and by a Grant-in-Aid for Scientific Research on Innovative Areas from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MS). ",

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T1 - Downregulation of POLD4 in Calu6 cells results in G1-S blockage through suppression of the Akt-Skp2-p27 pathway

AU - Huang, Qinmiao

AU - Suzuki, Motoshi

AU - Zeng, Yiming

AU - Zhang, Huaping

AU - Yang, Dongyong

AU - Lin, Huihuang

N1 - Funding Information: This work was supported by the National Natural Science Foundation of China (Grant No. 81141093 ), the Science Foundation of the Fujian Province, China (Grant No. 2013J01290 ) and by a Grant-in-Aid for Scientific Research on Innovative Areas from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (MS).

PY - 2014/4/1

Y1 - 2014/4/1

N2 - Previously, we have shown that downregulation of POLD4 in lung cancer cells delays progression through the G1-S cell cycle transition and leads to increased genomic instability. To date however, detailed molecular mechanisms have not been elucidated to explain how this occurs. In the present study, we found that reduction in POLD4 by siRNA knockdown promoted downregulation of both p-Akt Ser473 and Skp2 as well as upregulation of p27. Furthermore, these protein expression levels were rescued when siRNA-resistant POLD4 was ectopically expressed in the knockdown cells. These data suggest that the POLD4 downregulation is associated with impaired Akt-Skp2-p27 pathway in lung cancer.

AB - Previously, we have shown that downregulation of POLD4 in lung cancer cells delays progression through the G1-S cell cycle transition and leads to increased genomic instability. To date however, detailed molecular mechanisms have not been elucidated to explain how this occurs. In the present study, we found that reduction in POLD4 by siRNA knockdown promoted downregulation of both p-Akt Ser473 and Skp2 as well as upregulation of p27. Furthermore, these protein expression levels were rescued when siRNA-resistant POLD4 was ectopically expressed in the knockdown cells. These data suggest that the POLD4 downregulation is associated with impaired Akt-Skp2-p27 pathway in lung cancer.

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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 7

ER -

Downregulation of POLD4 in Calu6 cells results in G1-S blockage through suppression of the Akt-Skp2-p27 pathway

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