CoChat
Sign Up
Cited by 46Heat shock proteins researchUbiquitin and proteasome pathwaysAdvanced Proteomics Techniques and Applications

Novel Hsp90 partners discovered using complementary proteomic approaches

Open access
Tsaytler, Pavel A., Krijgsveld, Jeroen, Goerdayal, Soenita S., Rüdiger, Stefan, Egmond, Maarten R.·2009·Cell Stress and Chaperones
DOI 10.1007/s12192-009-0115-zPMC PMC2866955
Open this paper in CoChat — free accountOpen PDF

Abstract

Hsp90 is an essential eukaryotic molecular chaperone that stabilizes a large set of client proteins, many of which are involved in various cellular signaling pathways. The current list of Hsp90 interactors comprises about 200 proteins and this number is growing steadily. In this paper, we report on the application of three complementary proteomic approaches directed towards identification of novel proteins that interact with Hsp90. These methods are coimmunoprecipitation, pull down with biotinylated geldanamycin, and immobilization of Hsp90beta on sepharose. In all, this study led to the identification of 42 proteins, including 18 proteins that had not been previously characterized as Hsp90 interactors. These novel Hsp90 partners not only represent abundant protein species, but several proteins were identified at low levels, among which signaling kinase Cdk3 and putative transcription factor tripartite motif-containing protein 29. Identification of tetratricopeptide-repeat-containing mitochondrial import receptor protein Tom34 suggests the involvement of Hsp90 in the early steps of translocation of mitochondrial preproteins. Taken together, our data expand the knowledge of the Hsp90 interactome and provide a further step in our understanding of the Hsp90 chaperone system.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1007/s12192-009-0115-z

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Tom34 is found predominantly in the cytosol and binds Hsp90 and Hsp70, as does Tom70.

    “Although associated with mitochondria, Tom34 is found more predominantly in the cytosol and binds to the chaperone proteins Hsp90 and Hsp70, as does Tom70 (66–68).”

    From Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation (2011) · cites this paper as [67]

    The Discussion (page unavailable) describes Tom34 as a suggested cytosolic protein and reports that it forms complexes with Hsp90. It does not establish that Tom34 is predominantly cytosolic or that it binds Hsp70. The paper discusses Tom70’s interaction with Hsp90, but its only mention connecting Tom70 to Hsp70 is the title of a cited work in the References. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 34

  1. Caplan AJ, Mandal AK, Theodoraki MA (2007) Molecular chaperones and protein kinase quality control. Trends Cell Biol 17:87-92. doi:10.1016/j.tcb.2006.12.002 · DOI
  2. Chadli A, Felts SJ, Toft DO (2008) GCUNC45 is the first Hsp90 co- chaperone to show alpha/beta isoform specificity. J Biol Chem 283:9509-9512. doi:10.1074/jbc.C800017200 · DOI
  3. Citri A, Harari D, Shohat G, Ramakrishnan P, Gan J, Lavi S, Eisenstein M, Kimchi A, Wallach D, Pietrokovski S, Yarden Y (2006) Hsp90 recognizes a common surface on client kinases. J Biol Chem 281:14361-14369. doi:10.1074/jbc. · DOI
  4. M512613200 · DOI
  5. Crevel G, Bennet D, Cotteril S (2008) The human TPR protein TTC4 is a putative Hsp90 co-chaperone which interacts with Cdc6 and shows alterations in transformed cells. PLoS One 3:1-10. doi:10.1371/journal.pone.0001737 · DOI
  6. Falsone SF, Gesslbauer B, Tirk F, Piccinini A, Kungl AJ (2005) A proteomic snapshot of the human heat shock protein 90 interactome. FEBS Lett 579:6350-6354. doi:10.1016/j.febslet. 2005.10.020 · DOI
  7. Fan ACY, Bhangoo MK, Young JC (2006) Hsp90 functions in the targeting and outer membrane translocation steps of Tom70- mediated mitochondrial import. J Biol Chem 281:33313-33324. doi:10.1074/jbc.M605250200 · DOI
  8. Kosaka Y, Inoue H, Ohmachi T, Yokoe T, Matsumoto T, Minori K, Tanaka F, Watanabe M, Mori M (2007) Tripartite motif- containing 29 (TRIM29) is a novel marker for lymph node metastasis in gastric cancer. Ann Surg Oncol 14:2543-2549. doi:10.1245/s10434-007-9461-1 · DOI
  9. Lamphere L, Fiore F, Xu X, Brizuela L, Keezer S, Sardet C, Draetta GF, Gyuris J (1997) Interaction between Cdc37 and Cdk4 in human cells. Oncogene 14:1999-2004. doi:10.1038/sj.onc.1201036 · DOI
  10. Lotz GP, Brychzy A, Heinz S, Obermann WM (2008) J Cell Sci 121:717-723. doi:10.1242/jcs.015610 · DOI
  11. Modi S, Stopeck AT, Gordon MS, Mendelson D, Solit DB, Bagatell R, Ma W, Wheler J, Rosen N, Norton L, Cropp GF, Johnson RG, Hannah AL, Hudis CA (2007) Combination of trastuzumab and tanespimycin (17-AAG, KOS-953) is safe and active in trastuzumab-refractory HER-2 overexpressing breast cancer: a phase I dose-escalation study. J Clin Oncol 25(Modi, S., Stopeck, A.T., Gordon, M.S., Mendelson, D., Solit, D.B., Bagatell, R., Ma, W., Wheler, J., Rosen, N., Norton, L., Cropp, G.F., Johnson, R.G., Hannah, A.L., and Hudis, C.A):5410-5417. doi:10.1200/ JCO.2007.11.7960 · DOI
  12. Nisole S, Stoye JP, Saib A (2005) TRIM family proteins: retroviral restriction and antiviral defense. Nat Rev Microbiol 3:799-808. doi:10.1038/nrmicro1248 · DOI · Paper page
  13. Pearl LH, Prodromou C, Workman P (2008) The Hsp90 molecular chaperone: an open and shut case for treatment. Biochem J 410:439-453. doi:10.1042/BJ20071640 · DOI · Paper page
  14. Prince T, Matts RL (2004) Definition of protein kinase sequence that trigger high affinity binding of Hsp90 and Cdc37. J Biol Chem 279:39975-39981. doi:10.1074/jbc.M406882200 · DOI
  15. Ramalingam SS, Egorin MG, Ramanathan RK, Remick SC, Sikorski RP, Lagattuta TF, Chatta GS, Friedland dM, Stoller RG, Potter DM, Ivy SP, Belani CP (2008) A phase I study of 17-allylamino- 17-demethoxygeldanamycin combined with paclitaxel in patients with advanced solid malignancies. Clin Cancer Res 14:3456- 3461. doi:10.1158/1078-0432.CCR-07-5088 · DOI
  16. Richter K, Muschler P, Hainzl O, Reinstein J, Buchner J (2003) Sti1 is a non-competitive inhibitor of the Hsp90 ATPase. J Biol Chem 278:10328-10333. doi:10.1074/jbc.M213094200 · DOI
  17. Roe SM, Ali MMU, Meyer P, Vaughan CK, Panaretou B, Piper PW, Prodromou C, Pearl L (2004) The mechanism of Hsp90 regulation by the protein kinase-specific cochaperone p50cdc37. Cell 116:87-98. doi:10.1016/S0092-8674(03)01027-4 · DOI
  18. Rüdiger S, Freund SM, Verprintsev DB, Fersht AR (2002) CRINEPT- TROSY NMR reveals p53 core domain bound in an unfolded form to the chaperone Hsp90. Proc Natl Acad Sci U S A 99:11085-11090. doi:10.1073/pnas.132393699 · DOI
  19. Schlatter H, Langer T, Rosmus S, Onneken ML, Fasold H (2002) A novel function for the Hsp90 kDa heat-shock protein (Hsp90): facilitating nuclear export of 60 S ribosomal subunits. Biochem J 362:675-684. doi:10.1042/0264-6021:3620675 · DOI
  20. Schlegel T, Mirus O, von Haeseler A, Schleiff E (2007) The tetratricopeptide repeats of receptors involved in protein translo- cation across membranes. Mol Biol Evol 24:2763-2774. doi:10.1093/molbev/msm211 · DOI
  21. Schumacher JA, Crockett DK, Elenitoba-Johnson KSJ, Lim MS (2007) Proteome-wide changes induced by the Hsp90 inhibitor, geldanamycin in anaplastic large cell lymphoma cells. Proteomics 7:2603-2616. doi:10.1002/pmic.200700108 · DOI
  22. Shiau AK, Harris SF, Southworth DR, Agard DA (2006) Structural analysis of E. coli hsp90 reveals dramatic nucleotide-dependent conformational rearrangements. Cell 127:329-340. doi:10.1016/ j.cell.2006.09.027 · DOI · Paper page
  23. Sreedhar AS, Kalmar E, Csermely P, Shen YF (2004) Hsp90 isoforms: functions, expression and clinical importance. FEBS Lett 562:11-15. doi:10.1016/S0014-5793(04)00229-7 · DOI
  24. Stebbins CE, Russo AA, Schneider C, Rosen N, Hartl FU, Pavletich NP (1997) Crystal structure of an Hsp90-geldanamycin complex: targeting of a protein chaperone by an antitumor agent. Cell 89:239-250. doi:10.1016/S0092-8674(00)80203-2 · DOI
  25. Te J, Jia L, Rogers J, Miller A, Hartson SD (2007) Novel subunits of the mammalian Hsp90 signal transduction chaperone. J Prot Res 6:1963-1973. doi:10.1021/pr060595i · DOI
  26. Terasawa K, Yoshimatsu K, Iemura S, Natsume T, Tanaka K, Minami Y (2006) Cdc37 interacts with the glycine-rich loop of Hsp90 client kinases. Mol Cell Biol 26:3378-3389. doi:10.1128/ MCB.26.9.3378-3389.2006 · DOI
  27. Vaughan CK, Gohlke U, Sobott F, Good VM, Ali MMU, Prodromou C, Robinson CV, Saibil HR, Pearl LH (2006) Structure of an Hsp90-Cdc37-Cdk4 complex. Mol Cell 23:697-707. doi:10.1016/j.molcel.2006.07.016 · DOI
  28. Weinstein IB, Joe AK (2006) Mechanisms of disease: oncogene addiction-a rationale for molecular targeting in cancer therapy. Nat Clin Pract Oncol 3:448-457. doi:10.1038/ncponc0558 · DOI
  29. Yang CS, Weiner H (2002) Yeast two-hybrid screening identifies binding partners of human Tom34 that have ATPase activity and form a complex with Tom34 in the cytosol. Arch Biochem Biophys 400:105-110. doi:10.1006/abbi.2002.2778 · DOI · Paper page
  30. Ye X, Zhu C, Harper JW (2001) A premature-termination mutation in the Mus musculus cyclin-dependent kinase 3 gene. Proc Natl Acad Sci U S A 98:1682-1686. doi:10.1073/pnas.041596198 · DOI
  31. Young JC, Obermann WMJ, Hartl FU (1998) Specific binding of tetratricopeptide repeat proteins to the C-terminal 12-kDa domain of Hsp90. J Biol Chem 273:18007-18010. doi:10.1074/ jbc.273.29.18007 · DOI
  32. Young JC, Hoogenraad NJ, Hartl FU (2003) Molecular chaperones Hsp90 and Hsp70 deliver preproteins to the mitochondrial import receptor Tom70. Cell 112:41-50. doi:10.1016/S0092-8674(02) 01250-3 · DOI · Paper page
  33. Zhao R, Davey M, Hsu Y, Kaplanek P, Tong A, Parsons AB, Krogan N, Cagney G, Mai D, Greenblatt J, Boone C, Emili A, Houry WA (2005) Navigating the chaperone network: an integrative map of physical and genetic interactions mediated by the Hsp90 chaperone. Cell 120:715-727. doi:10.1016/j.cell.2004.12.024 · DOI · Paper page
  34. Zhao R, Kakihara Y, Gribun A, Huen J, Yang G, Khanna M, Costanzo M, Brost RL, Boone C, Hughes TR, Yip CM, Houry WA (2008) Molecular chaperone Hsp90 stabilizes Pih1/Nop17 to maintain R2TP complex activity that regulates snoRNA accumulation. J Cell Biol 180:563-578. doi:10.1083/jcb.200709061 · DOI

Cited by

Sorted by citations

Authors
Tsaytler, P. A., Krijgsveld, J., Goerdayal, S. S., Rüdiger, S., & Egmond, M. R.
Affiliations
Utrecht University (NL)
Corresponding author
Tsaytler, Pavel A.
ORCID
Venue
Cell Stress and Chaperones
Publisher
Elsevier BV
Published
2009-11
Volume
14
Issue
6
Pages
629-638
ISSN
1355-8145 (ISSN-L)
DOI
10.1007/s12192-009-0115-z
PMC
PMC2866955
OpenAlex
W1970847499
Cited by
46
References
4
Citations by year
2025: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2019: 7 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 4 · 2012: 5
FWCI
2.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Stress and Chaperones (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Utrecht University Repository (Utrecht University) (submittedVersion)
Funders
  • Universiteit Utrecht
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
Keywords
HSP90, protein-protein interaction, molecular chaperones, CDK3, mitochondrial import receptor
MeSH terms
Mitochondrial Precursor Protein Import Complex Proteins, DNA-Binding Proteins, Humans, Protein Binding, Transcription Factors, Consensus Sequence, HSP90 Heat-Shock Proteins, Amino Acid Motifs, Mitochondrial Membrane Transport Proteins, Proteomics, Cell Line, Tumor, Immunoprecipitation, Cyclin-Dependent Kinase 3

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review