Nuclear translocation of HB-EGF-C. Membrane-anchored heparin-binding epidermal growth factor-like growth factor (proHB-EGF) yields soluble HB-EGF (sHB-EGF) and a carboxy-terminal fragment of HB-EGF (HB-EGF-CTF) after ectodomain shedding. sHB-EGF binds to EGFR as a ligand and activates the downstream signal pathways. HB-EGF-CTF translocates from plasma membrane to the nucleus after shedding and the cytoplasmic domain of HB-EGF (HB-EGF-C) binds to some transcriptional repressors in the nucleus. Moreover, unshed proHB-EGF translocates to the nucleus after shedding stimuli. HB-EGF-C is included in both HB-EGF-CTF and proHB-EGF.