Inhibition of nuclear import by protein kinase B (Akt) regulates the subcellular distribution and activity of the forkhead transcription factor AFX

Molecular and Cellular Biology
A M BrownawellBoudewijn M T Burgering

Abstract

AFX belongs to a subfamily of Forkhead transcription factors that are phosphorylated by protein kinase B (PKB), also known as Akt. Phosphorylation inhibits the transcriptional activity of AFX and changes the steady-state localization of the protein from the nucleus to the cytoplasm. Our goal was threefold: to identify the cellular compartment in which PKB phosphorylates AFX, to determine whether the nuclear localization of AFX plays a role in regulating its transcriptional activity, and to elucidate the mechanism by which phosphorylation alters the localization of AFX. We show that phosphorylation of AFX by PKB occurs in the nucleus. In addition, nuclear export mediated by the export receptor, Crm1, is required for the inhibition of AFX transcriptional activity. Both phosphorylated and unphosphorylated AFX, however, bind Crm1 and can be exported from the nucleus. These results suggest that export is unregulated and that phosphorylation by PKB is not required for the nuclear export of AFX. We show that AFX enters the nucleus by an active, Ran-dependent mechanism. Amino acids 180 to 221 of AFX comprise a nonclassical nuclear localization signal (NLS). S193, contained within this atypical NLS, is a PKB-dependent phosphorylation si...Continue Reading

References

Dec 11, 1991·Proceedings of the National Academy of Sciences of the United States of America·S Ziemin-van der PoelJ D Rowley
May 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·P F JonesB A Hemmings
Sep 1, 1989·Gene Analysis Techniques·K Zerivitz, G Akusjärvi
Jul 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·S P Staal
May 9, 1995·Proceedings of the National Academy of Sciences of the United States of America·U M MollG Riou
Feb 28, 1995·Proceedings of the National Academy of Sciences of the United States of America·F R BischoffH Ponstingl
Sep 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·J CorralA Karpas
May 28, 1996·Proceedings of the National Academy of Sciences of the United States of America·J L BennicelliF G Barr
Sep 3, 1996·Proceedings of the National Academy of Sciences of the United States of America·S ScheidlerP K Vogt
Mar 15, 1997·Genes & Development·S G KennedyN Hay
Aug 1, 1997·Molecular Biology of the Cell·M J De VitM Johnston
Oct 6, 1997·Science·B Ossareh-NazariC Dargemont
Oct 23, 1997·Proceedings of the National Academy of Sciences of the United States of America·Z SongyangT F Franke
Oct 23, 1997·Journal of the National Cancer Institute·C L SchlampR W Nickells
Dec 31, 1997·The Journal of Biological Chemistry·R MeierB A Hemmings
Feb 12, 1998·The Journal of Biological Chemistry·M AndjelkovićB A Hemmings
Mar 25, 1998·Current Biology : CB·G J ArtsI W Mattaj
Oct 6, 1998·Annual Review of Biochemistry·I W Mattaj, L Englmeier

❮ Previous
Next ❯

Citations

Jul 13, 2006·Naunyn-Schmiedeberg's Archives of Pharmacology·Frank J TamarkinRobert M Weiss
Sep 1, 2005·Apoptosis : an International Journal on Programmed Cell Death·T S SchwabE L Feldman
Jun 26, 2010·Journal of Cardiovascular Translational Research·Anwarul FerdousJoseph A Hill
May 5, 2005·Neurochemistry International·Vandana M SharmaTaranath K Shetty
Jul 26, 2002·Archives of Biochemistry and Biophysics·Karen C Arden, William H Biggs
Nov 19, 2002·Biochemical and Biophysical Research Communications·Honoka AraiKinuko Mitani
Mar 21, 2003·Biochemical and Biophysical Research Communications·Osvaldo ReyEnrique Rozengurt
Mar 8, 2002·Cellular Signalling·Karleen M Nicholson, Neil G Anderson
Jul 13, 2002·Trends in Biochemical Sciences·Boudewijn M T Burgering, Geert J P L Kops
Feb 5, 2003·Drug Discovery Today·Tweeny R Kau, Pamela A Silver
Oct 19, 2002·Biochimica Et Biophysica Acta·Luca M NeriAlberto M Martelli
Jul 10, 2012·Biochemistry·Janusz J PetkowskiIan G Macara
Aug 25, 2009·Nature Immunology·Stephen M Hedrick
Jan 21, 2004·Nature Reviews. Cancer·Tweeny R KauPamela A Silver
Dec 13, 2005·Nature Reviews. Cancer·Andreas G BaderPeter K Vogt
May 25, 2007·Nature Reviews. Molecular Cell Biology·Armando van der Horst, Boudewijn M T Burgering
Jan 18, 2013·Nature Reviews. Molecular Cell Biology·Astrid Eijkelenboom, Boudewijn M T Burgering
Apr 9, 2008·Oncogene·D R Calnan, A Brunet
Apr 9, 2008·Oncogene·Z Fu, D J Tindall
Apr 9, 2008·Oncogene·B M Th Burgering
May 3, 2002·Immunology·Doreen A Cantrell
Feb 13, 2008·Proceedings of the National Academy of Sciences of the United States of America·Brooke M EmerlingNavdeep S Chandel
May 7, 2009·The Journal of Biological Chemistry·Jan SilhanTomas Obsil
Dec 8, 2004·The Journal of Biological Chemistry·Maya T KunkelAlexandra C Newton
May 14, 2005·Antioxidants & Redox Signaling·Yoko Furukawa-HibiNoboru Motoyama
Jun 10, 2009·Antioxidants & Redox Signaling·Ehab H SarsourPrabhat C Goswami
Sep 30, 2010·Antioxidants & Redox Signaling·Anna A SzypowskaBoudewijn M T Burgering
Jul 14, 2010·Antioxidants & Redox Signaling·Maaike C W van den Berg, Boudewijn M T Burgering
Mar 13, 2009·Cardiovascular Research·Shigeki MiyamotoMark A Sussman
Jul 28, 2006·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Erik EdströmBrun Ulfhake
Jun 1, 2009·Current Opinion in Lipidology·Janet D Sparks, Henry H Dong
Oct 19, 2005·Genes & Development·Oscar Puig, Robert Tjian
Mar 4, 2006·Development, Growth & Differentiation·Gema C ManuelHans R Bode
Jan 4, 2008·Acta Physiologica·E L Greer, A Brunet
Jan 6, 2005·Science's STKE : Signal Transduction Knowledge Environment·Jun O Liu

❮ Previous
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