Hsp90 and co-chaperones twist the functions of diverse client proteins.
Hsp90 molecular chaperones are required for the stability and activity of a diverse range of client proteins that have critical roles in signal transduction, cellular trafficking, chromatin remodeling, cell growth, differentiation, and reproduction. Mammalian cells contain three types of Hsp90s: cytosolic Hsp90, mitochondrial Trap-1, and Grp94 of the endoplasmic reticulum. Each of the Hsp90s, as well as the bacterial homolog, HtpG, hydrolyze ATP and undergo similar conformational changes. Unlike the other forms of Hsp90, cytosolic Hsp90 function is dependent on a battery of co-chaperone proteins that regulate the ATPase activity of Hsp90 or direct Hsp90 to interact with specific client proteins. This review will summarize what is known about Hsp90's ability to mediate the folding and activation of diverse client proteins that contribute to human diseases, such as cancer and fungal and viral infections.
Zuehlke
Abbey
A
Department of Microbiology, Molecular Biology and Biochemistry and the Center for Reproductive Biology, University of Idaho, Moscow, ID 83844-3052, USA.
Johnson
Jill L
JL
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism*
D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; D020033:Protein Isoforms; D000251:Adenosine Triphosphatases
Mol Cell Biol. 2007 Jan;27(2):768-76
17101799
J Biol Chem. 2004 May 28;279(22):23267-73
15044454
Cell. 2007 Oct 19;131(2):257-70
17956728
Biochem J. 2008 Jul 15;413(2):261-8
18412542
Mol Cell. 2008 Dec 5;32(5):631-40
19061638
Mol Cell. 2006 Sep 1;23(5):697-707
16949366
EMBO J. 2008 Oct 22;27(20):2789-98
18818696
Cell Stress Chaperones. 2009 Jan;14(1):83-94
18636345
J Biol Chem. 1998 Dec 25;273(52):35194-200
9857057
Nat Rev Cancer. 2005 Oct;5(10):761-72
16175177
Nat Struct Mol Biol. 2009 Mar;16(3):235-6
19259122
Exp Biol Med (Maywood). 2003 Feb;228(2):111-33
12563018
Trends Cell Biol. 2007 Feb;17(2):87-92
17184992
Annu Rev Biochem. 2006;75:271-94
16756493
Cell Stress Chaperones. 2007 Winter;12(4):353-63
18229454
Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2818-23
19196973
Nat Cell Biol. 2001 Jan;3(1):93-6
11146632
Int J Biochem Cell Biol. 2008;40(11):2358-62
17951098
Biochem J. 2008 Mar 15;410(3):439-53
18290764
Nature. 1998 Nov 26;396(6709):336-42
9845070
J Biol Chem. 1999 Sep 17;274(38):26654-60
10480867
EMBO J. 1999 Feb 1;18(3):754-62
9927435
Biochemistry. 2008 Aug 5;47(31):8203-13
18620420
J Mol Biol. 2009 Jul 10;390(2):278-91
19427321
Rev Physiol Biochem Pharmacol. 2004;151:1-44
14740253
J Biol Chem. 2000 Nov 3;275(44):34140-6
10942767
Mol Cell. 2007 Jan 12;25(1):151-9
17218278
Cell. 2006 Nov 17;127(4):803-15
17110338
Biosci Biotechnol Biochem. 2008 May;72(5):1394-7
18460784
Crit Rev Biochem Mol Biol. 2007 Sep-Oct;42(5):355-72
17917872
Nature. 2003 Sep 25;425(6956):407-10
14508491
EMBO J. 2009 Feb 4;28(3):234-47
19131964
EMBO J. 2004 Feb 11;23(3):511-9
14739935
Crit Rev Biochem Mol Biol. 2004 Sep-Dec;39(5-6):279-95
15763706
Science. 2005 Sep 30;309(5744):2185-9
16195452
Cell Stress Chaperones. 2007 Spring;12(1):1-8
17441502
Nature. 2006 Apr 20;440(7087):1013-7
16625188
Nat Immunol. 2007 May;8(5):497-503
17435760
Cell Res. 2006 Sep;16(9):742-9
16940964
Mol Microbiol. 2000 Jun;36(6):1360-70
10931286
Anticancer Res. 2009 Mar;29(3):797-807
19414312
Mol Endocrinol. 1995 Jun;9(6):670-8
8592513
Nature. 2002 Jun 6;417(6889):618-24
12050657
Mol Biol Cell. 2008 Dec;19(12):5249-58
18829866
Genes Dev. 2007 Jan 15;21(2):195-205
17234885
J Biol Chem. 2008 Jul 4;283(27):18473-7
18442971
Nat Cell Biol. 2008 Mar;10(3):272-82
18264092
Mol Endocrinol. 2007 Dec;21(12):2956-67
17717070
J Biol Chem. 2002 Apr 5;277(14):11873-81
11809754
Cell. 2007 Oct 5;131(1):121-35
17923092
Cell. 2005 Mar 11;120(5):715-27
15766533
Invest Ophthalmol Vis Sci. 2008 Jul;49(7):2878-87
18408180
Cell. 1995 Nov 17;83(4):589-98
7585962
Nat Genet. 2003 Jan;33(1):70-4
12483213
Cancer Res. 2008 Jan 15;68(2):589-96
18199556
Mol Cell Biol. 2001 Apr;21(7):2594-607
11259606
Mol Cell Biol. 1998 Dec;18(12):7353-9
9819422
Mol Cell Biol. 2006 Mar;26(5):1722-30
16478993
Nat Struct Mol Biol. 2009 Jan;16(1):2-6
19125165