CDK1 promotes cell proliferation and survival via phosphorylation and inhibition of FOXO1 transcription factor

Oncogene
P LiuHaojie Huang

Abstract

The forkhead box O (FOXO) transcription factor FOXO1 functions as a tumor suppressor by regulating expression of genes involved in apoptosis, cell cycle arrest and oxidative detoxification. Here, we demonstrate that cyclin-dependent kinase 1 (CDK1) specifically phosphorylates FOXO1 at serine 249 (S249) in vitro and in vivo. Coimmunoprecipitation assays demonstrate that both endogenous CDK1 and ectopically expressed CDK1 form a protein complex with FOXO1 in prostate cancer (PCa) cells. In vitro protein binding assays reveal that CDK1 interacts directly with FOXO1. Accordingly, overexpression of CDK1 inhibits the transcriptional activity of FOXO1 in PCa cells through S249 phosphorylation on FOXO1. Consistent with the roles of FOXO3a and FOXO4 (two other members of the FOXO family) in cell cycle regulation, forced expression of FOXO1 causes a delay in the transition from G2 to M phase. This effect is blocked completely by overexpression of CDK1 and cyclin B1. Ectopic expression of constitutively active CDK1 also inhibits FOXO1-induced apoptosis in PCa cells. Moreover, we demonstrate that the inhibitory effect of FOXO1 on Ras oncogene-induced colony formation in fibroblasts is diminished by overexpression of CDK1. Given that CDK1 a...Continue Reading

References

Apr 29, 1998·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·B V KallakuryJ S Ross
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·X WuC L Sawyers
Jun 8, 1999·The Journal of Biological Chemistry·E D TangK L Guan
Jun 8, 1999·The Journal of Biological Chemistry·G RenaP Cohen
Jun 23, 1999·Proceedings of the National Academy of Sciences of the United States of America·W H BiggsK C Arden
Aug 10, 2001·The Journal of Biological Chemistry·H HuangD J Tindall
Mar 9, 2002·Molecular and Cellular Biology·Geert J P L KopsBoudewijn M T Burgering
May 8, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marie StahlRené H Medema
Jun 6, 2002·The Journal of Biological Chemistry·Yoko Furukawa-HibiNoboru Motoyama
Jun 28, 2002·Cancer Cell·Douglas R Green, Gerard I Evan
Aug 2, 2002·Cancer Cell·Shivapriya RamaswamyWilliam R Sellers
Sep 19, 2002·Trends in Pharmacological Sciences·Marie KnockaertLaurent Meijer
Oct 23, 2002·Molecular and Cellular Biology·Marc SchmidtRené H Medema
Jan 9, 2003·The Journal of Biological Chemistry·David R Plas, Craig B Thompson
Jan 21, 2003·American Journal of Human Genetics·Xiangyang DongWanguo Liu
Sep 19, 2003·Proceedings of the National Academy of Sciences of the United States of America·Hitomi MatsuzakiAkiyoshi Fukamizu
Sep 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Masahiro AokiPeter K Vogt
Nov 17, 2004·Genes & Development·Charles J Sherr, James M Roberts
Jan 26, 2005·Proceedings of the National Academy of Sciences of the United States of America·Haojie HuangDonald J Tindall
Jul 8, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mustafa Ozen, Michael Ittmann
Jul 13, 2006·Human Mutation·Xianglin WuJunjie Chen
Aug 19, 2006·Science·Julie M PinkstonCynthia Kenyon
Oct 18, 2006·Proceedings of the National Academy of Sciences of the United States of America·Shaoyong ChenSteven P Balk

❮ Previous
Next ❯

Citations

Feb 9, 2012·Journal of Proteome Research·Stephanie M PützAlbert Sickmann
Jan 18, 2013·Nature Reviews. Molecular Cell Biology·Astrid Eijkelenboom, Boudewijn M T Burgering
Jul 24, 2010·Antioxidants & Redox Signaling·Stephen S MyattEric W-F Lam
Jul 14, 2010·Antioxidants & Redox Signaling·Oscar Puig, Jaakko Mattila
Jul 14, 2010·Antioxidants & Redox Signaling·Maaike C W van den Berg, Boudewijn M T Burgering
Sep 18, 2012·Antioxidants & Redox Signaling·Paraskevi Charitou, Boudewijn M T Burgering
Dec 10, 2009·Cancer Research·Liang WangStephen N Thibodeau
Nov 22, 2013·PloS One·Annika FendlerGeorge M Yousef
Jul 2, 2010·Oxidative Medicine and Cellular Longevity·Kenneth MaieseYan Chen Shang
Aug 3, 2013·Cellular and Molecular Life Sciences : CMLS·Seungmin LeeHyeseong Cho
Sep 17, 2014·International Journal of Molecular Sciences·Alhassan HameedaldeenDana T Graves
Mar 10, 2015·Cellular Signalling·Hong JianShun Lu
Jan 5, 2016·Immunologic Research·Carsten BergesHermann Einsele
May 4, 2011·Cell Proliferation·X Hu, L C Moscinski
Feb 18, 2014·Biochimica Et Biophysica Acta·Shao-An WangJan-Jong Hung
Mar 29, 2011·Biochimica Et Biophysica Acta·Xinbo ZhangArun K Rishi
Feb 26, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·K BednarekM Jarmuz-Szymczak
Feb 20, 2019·Journal of Molecular Endocrinology·Junye ChenQiren Huang
Jun 8, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Hao ChenJoshua F Robinson
Jun 5, 2018·Oncotarget·Mehran KarimzadehYasser Riazalhosseini

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Shaoyong ChenSteven P Balk
Proceedings of the National Academy of Sciences of the United States of America
Hitomi MatsuzakiAkiyoshi Fukamizu
© 2022 Meta ULC. All rights reserved