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

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1780-1783
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	24
Issue number	7
DOIs	https://doi.org/10.1016/j.bmcl.2014.02.033
Publication status	Published - 01-04-2014
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2014.02.033

Cite this

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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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doi = "10.1016/j.bmcl.2014.02.033",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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TY - JOUR

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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UR - https://www.scopus.com/pages/publications/84897438803#tab=citedBy

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DO - 10.1016/j.bmcl.2014.02.033

M3 - Article

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AN - SCOPUS:84897438803

SN - 0960-894X

VL - 24

SP - 1780

EP - 1783

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

Abstract

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All Science Journal Classification (ASJC) codes

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