The suggestion of causative involvement of the molecular chaperones in the process of cellular immortalization in vitro is based on the following observations.
1) Current immortalization procedures, as transfect ion with c-myc, h-TERT or DNA-viral T-proteins or exposure to mutagens, require an increase in the expression of the molecular chaperones.
2) Downregulation of the molecular chaperones Hsp70 or Hsp 90 in immortalized cells leads to apoptotic cell death.
3) Maintenance of telomere length as obtained by transfection with h-TERT is not in itself sufficient for the attainment of cellular immortalization. Possibly a mutational hyperexpression of the associated Hsp90 is required.
4)The DNA-viral T-proteins are molecular chaperones with a DNA-binding alpha-helix motive shared by c-myc and essential for their immortalizing effects.
5) The DEAD-box motive of the sv40 T-protein suggests a DNA/RNA chaperone function.
6) The sv40 T-protein and c-myc shows nuclear co localisation with Hsp70 and causes an increase in the expression of Hsp70.
7) The basal level of Hsp70 is relatively high in the constituently immortal cells from catfish.
Conclusion: An increase in the expression of the molecular chaperones is a common denominator in cellular immortalization in vitro. Possibly the concerted action of different selected DNA/RNA and protein chaperones is required.