Proteolytic release of the carboxy-terminal fragment of proHB-EGF causes nuclear export of PLZF. J Cell Biol 2003 Nov 10;163(3):489-502
Date
11/05/2003Pubmed ID
14597771Pubmed Central ID
PMC2173632DOI
10.1083/jcb.200303017Scopus ID
2-s2.0-0242425875 (requires institutional sign-in at Scopus site) 141 CitationsAbstract
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.
Author List
Nanba D, Mammoto A, Hashimoto K, Higashiyama SAuthor
Akiko Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Active Transport, Cell NucleusAnimals
Cell Line
Cell Membrane
Cell Nucleus
Cyclin A
DNA-Binding Proteins
Epidermal Growth Factor
Female
Genes, Regulator
Heparin-binding EGF-like Growth Factor
Humans
Hyperplasia
Intercellular Signaling Peptides and Proteins
Keratinocytes
Kruppel-Like Transcription Factors
Mice
Mice, Inbred C57BL
Peptide Hydrolases
Promyelocytic Leukemia Zinc Finger Protein
Protein Precursors
Protein Structure, Tertiary
Repressor Proteins
S Phase
Signal Transduction
Skin
Transcription Factors
