The Hsp90-FKBP51 heterocomplex in cancer development and progression

GALIGNIANA MD

Munich

Conferencia; Annual Period of Conferences of the Max-Planck Institute of Psychiatry of Munich; 2016

FKBP51 is an Hsp90-binding immunophilin that was first discovered associated to steroid receptors thanks to its association to Hsp90 dimers via tetratricopeptide repeats (TPR). FKBP51 occupies the empty receptor and is replaced by dynein-interacting factors such as FKBP52 or PP5 in a hormone-dependent manner, thus favoring the receptor retrotransport and also, its nuclear retention. Although in some studies is still under discussion what the real stoiquiometry of the interaction between Hsp90 and TPR-domain immunophilins is, there is a general consensus that in the physiological milieu of the cell, there is only one TPR protein bound per dimer of Hsp90. Here it will be discussed the biological relevance of the Hsp90-immunophilin heterocomplex in apoptosis, cancer development and progression, telomerase activity, and nuclear architecture rearrangement. In all of these basic biological situations, the properties shown by the Hsp90-immunophilin chaperone heterocomplex in the cell supports the existence of a single Hsp90-binding immunophilin bound per Hsp90 dimer, which can be dynamically exchanged by other TPR protein in a mutually exclusive fashion. In view of the number and relevance of signalling cascades and cellular events affected by this heterocomplex, the potential use of drugs with therapeutic purposes that may affect the organization and function of this protein oligomeric complex is currently analyzed.