JCB logo
Avanti Polar Lipids, Inc.
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 3 November 2003. doi:10.1083/jcb.200303017
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 965K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nanba, D.
Right arrow Articles by Higashiyama, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nanba, D.
Right arrow Articles by Higashiyama, S.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*Substance via MeSH
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

© The Rockefeller University Press, 0021-9525/2003/11/489 $8.00
The Journal of Cell Biology, Volume 163, Number 3, 489-502

Article

Proteolytic release of the carboxy-terminal fragment of proHB-EGF causes nuclear export of PLZF



Daisuke Nanba1, Akiko Mammoto1, Koji Hashimoto2 and Shigeki Higashiyama1

1 Department of Medical Biochemistry, Ehime University School of Medicine, Ehime 791-0295, Japan
2 Department of Dermatology, Ehime University School of Medicine, Ehime 791-0295, Japan

Address correspondence to Shigeki Higashiyama, Dept. of Medical Biochemistry, Ehime University School of Medicine, Shitsukawa, Shigenobu-cho, Onsen-gun, Ehime 791-0295, Japan. Tel.: 81-89-960-5253. Fax: 81-89-960-5256. email: shigeki{at}m.ehime-u.ac.jp

Cleavage of membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) via metalloprotease activation yields amino- and carboxy-terminal regions (HB-EGF and HB-EGF-C, respectively), with HB-EGF widely recognized as a key element of epidermal growth factor receptor transactivation in G protein–coupled receptor signaling. Here, we show a biological role of HB-EGF-C in cells. Subsequent to proteolytic cleavage of proHB-EGF, HB-EGF-C translocated from the plasma membrane into the nucleus. This translocation triggered nuclear export of the transcriptional repressor, promyelocytic leukemia zinc finger (PLZF), which we identify as an HB-EGF-C binding protein. Suppression of cyclin A and delayed entry of S-phase in cells expressing PLZF were reversed by the production of HB-EGF-C. These results indicate that released HB-EGF-C functions as an intracellular signal and coordinates cell cycle progression with HB-EGF.

Key Words: HB-EGF; ADAM12; shedding; PLZF; transcriptional repression

A. Mammoto's present address is Department of Surgical Research, Children's Hospital, Boston, MA 02115.

Abbreviations used in this paper: ADAM, a disintegrin and metalloprotease; EGFR, epidermal growth factor receptor; GPCR, G protein–coupled receptor; HB-EGF, heparin-binding EGF-like growth factor; PLZF, promyelocytic leukemia zinc finger; proHB-EGF, membrane-anchored heparin-binding EGF-like growth factor; TPA, 12-O-tetradecanoylphorbol-13-acetate.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents