Functions of the Hsp90-Binding FKBP Immunophilins - The Networking of Chaperones by Co-chaperones - page 56

Summary
In addressing the physiological importance of PPIases, Heitman and colleagues
(Dolinski et al. 1997 ) generated an S. cerevisiae strain that lacked all 12 PPIase
genes in the FKBP and cyclophilin families; the pluri-mutant strain displayed some
growth abnormalities but was viable, thus demonstrating that these genes collec-
tively are non-essential in yeast. Nonetheless, it has become increasingly clear that
the Hsp90-binding FKBP immunophilins, through interactions with steroid recep-
tors, kinases, and other cellular factors, play important physiological and patho-
logical roles in mammals. Significant progress has been made on the elucidation of
these roles and the definition of underlying molecular mechanisms. The identifica-
tion of specific inhibitors will likely quicken in the coming few years and lead to
therapeutic targeting of individual Hsp90-associated FKBP immunophilins for the
treatment of a variety of human diseases.
Acknowledgements Studies in the authors' laboratory were supported by grants to the Border
Biomedical Research Center from the National Center for Research Resources (5 G12 RR008124)
and from the National Institute on Minority Health and Health Disparities (8 G12 MD007592)
from the National Institutes of Health. The authors were also supported in part by the Cancer
Prevention and Research Institute of Texas by grant number RP110444-P2 (M.B.C). M.D.G. was
supported by grants PICT 2011-1715, UBACYT 2011-14-GC, and the Fundaci￳n Roemmers.
The text in this chapter contains sections reproduced with kind permission from Springer Science
+ Business Media: Networking of Chaperones by Co-chaperones; Chapter 2: Functions of the
Hsp90-Binding FKBP Immunophilins; 2006; page 13-21; Marc B. Cox and David F. Smith
References
Abukhdeir AM, Vitolo MI, Argani P, De Marzo AM, Karakas B, Konishi H, Gustin JP, Lauring J,
Garay JP, Pendleton C, Konishi Y, Blair BG, Brenner K, Garrett-Mayer E, Carraway H, Bach-
man KE, Park BH (2008) Tamoxifen-stimulated growth of breast cancer due to p21 loss. Proc
Natl Acad Sci U S A 105(1):288-293
Bai X, Ma D, Liu A, Shen X, Wang QJ, Liu Y, Jiang Y (2007) Rheb activates mTOR by antagoniz-
ing its endogenous inhibitor, FKBP38. Science 318(5852):977-980
Banasavadi-Siddegowda YK, Mai J, Fan Y, Bhattacharya S, Giovannucci DR, Sanchez ER,
Fischer G, Wang X (2011) FKBP38 peptidylprolyl isomerase promotes the folding of cys-
tic fibrosis transmembrane conductance regulator in the endoplasmic reticulum. J Biol Chem
286(50):43071-43080
Barent RL, Nair SC, Carr DC, Ruan Y, Rimerman RA, Fulton J, Zhang Y, Smith DF (1998) Analy-
sis of FKBP51/FKBP52 chimeras and mutants for Hsp90 binding and association with proges-
terone receptor complexes. Mol Endocrinol 12(3):342-354
Barnham KJ, Bush AI (2008) Metals in Alzheimer's and Parkinson's diseases. Curr Opin Chem
Biol 12(2):222-228. doi:10.1016/j.cbpa.2008.02.019
Barth S, Edlich F, Berchner-Pfannschmidt U, Gneuss S, Jahreis G, Hasgall PA, Fandrey J, Wenger
RH, Camenisch G (2009) Hypoxia-inducible factor prolyl-4-hydroxylase PHD2 protein abun-
dance depends on integral membrane anchoring of FKBP38. J Biol Chem 284(34):23046-
23058