Figure 6

Model of endonuclein functions. Endonuclein may modulate several signal transduction pathways to the nucleus as well as chaperone activities in the ER. Through interaction with TIP-1, endonuclein may interfere with the Rho signaling pathway and the pathway leading to oncogenesis by Tax. RhoA, rhotekin and TIP-1 may form a ternary complex in the cytosol (indicated with two-way green arrows) that produces a signal in the nucleus increasing c-fos transcription (indicated with one-way green arrows). Tax may trans-activate a number of genes, e.g. c-fos (red arrows) through interaction with a number of cellular proteins. IL-6 stimulation activates two signaling pathways one involving the Janus kinases (Jaks) and one involving the MAP kinase cascade. The Jaks phosphorylate stat-3, which is then translocated into the nucleus. Usually, stat-3 then binds to the IL-6 response element (IL-6 RE), however, this does not occur at the Aα fibrinogen promoter that instead binds the transcription factor P16 (mt-SSB). The IL-6 induced transcription of Aα fibrinogen may thus be modulated by interaction of endonuclein with P16. In the ER endonuclein may modulate chaperone activities by interacting with the membrane bound co-chaperone HEJD (DNAJB11) and the chaperone BiP. The significance of the interaction of endonuclein with EIP-8 (SDF2-like protein 1) and PSGs (PSBGs) in the ER is unknown at present. Two-way arrows indicate putative protein-protein interactions. Protein motifs or domains are indicated on the proteins, MIR, RGD, PDB, J, PDZ, SSB and NLS.