Stress-induced-phosphoprotein 1 explained

Stress-induced-phosphoprotein 1 also Hsp70-Hsp90 organising protein (Hop) is encoded in the human by the STIP1 gene. It functions as a co-chaperone which reversibly links together the protein chaperones Hsp70 and Hsp90.^[1]

STI1 belongs to the large group of co-chaperones, which regulate and assist the major chaperones (mainly heat shock proteins). It is one of the best studied co-chaperones of the Hsp70-Hsp90 complex. It was first discovered in yeast and homologues were identified in humans, mice, rats, insects, plants, parasites, and viruses. The family of these proteins is referred to as STI1 (stress inducible protein) and can be divided into yeast, plant, and animal STI1 (Hop).

Synonyms

Hop Hsc70/Hsp90-organizing protein NY-REN-11 antigen P60

STI1 STI1L STIP1 Transformation-sensitive protein IEF-SSP-3521

Gene

STIP1 is located on chromosome 11q13.1 and consists of 14 exons.

Structure

STI proteins are characterized by some structural features: All homologues have nine tetratricopeptide repeat (TPR) motifs, that are clustered into domains of three TPRs. The TPR motif is a very common structural feature used by many proteins and provides the ability of directing protein-protein interactions. Crystallographic structural information is available for the N-terminal TPR1 and the central TPR2A domains in complex with Hsp90 resp. Hsp70 ligand peptides.^[2]

The Hsp70-Hsp90 Organizing Protein (Hop, STIP1 in humans) is the co-chaperone responsible for the transfer of client proteins between Hsp70 and Hsp90. Hop is evolutionarily conserved in Eukaryotes and is found in both the nucleus and cytoplasm.^[3] Drosophila Hop is a monomeric protein that consists of three tetratricopeptide repeat domain regions (TPR1, TPR2A, TPR2B), one aspartic acid-proline repeat domain (DP). The TPR domains interact with the c-terminals of Hsp90 and Hsp70, with TPR1 and TPR2B binding to Hsp70 and TPR2A binding preferentially to Hsp90. The intermediate structures of heat shock machinery are difficult to characterize completely because of the transient and fast paced nature of chaperone function.^[4]

Function

The main function of Hop is to link Hsp70 and Hsp90 together. But recent investigations indicate that it also modulates the chaperone activities of the linked proteins and possibly interacts with other chaperones and proteins. Apart from its role in the Hsp70/Hsp90 "chaperone machine" it seems to participate in other protein complexes too (for example in the signal transduction complex EcR/USP and in the Hepatitis B virus reverse transcriptase complex, which enables the viral replication). It acts as a receptor for prion proteins too.^{[5] [6]} Hop is located in diverse cellular regions and also moves between the cytoplasm and the nucleus.

In Drosophila RNA interference pathways, Hop has been shown to be an integral part of the pre-RISC complex for siRNAs.^[7] In the Drosophila Piwi-interacting RNA pathway, the RNA interference pathway responsible for the repression of transposable elements (transposons), Hop has been shown to interact with Piwi,^[8] and in the absence of Hop, transposons are derepressed, leading to severe genomic instability and infertility.^[9]

Interactions

STI1 has been shown to interact with PRNP^[10] and Heat shock protein 90kDa alpha (cytosolic), member A1.^{[11] [12]}

Further reading

• Rasmussen HH, van Damme J, Puype M, Gesser B, Celis JE, Vandekerckhove J . Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes . Electrophoresis . 13 . 12 . 960–9 . December 1992 . 1286667 . 10.1002/elps.11501301199 . 41855774 .
• Honoré B, Leffers H, Madsen P, Rasmussen HH, Vandekerckhove J, Celis JE . Molecular cloning and expression of a transformation-sensitive human protein containing the TPR motif and sharing identity to the stress-inducible yeast protein STI1 . The Journal of Biological Chemistry . 267 . 12 . 8485–91 . April 1992 . 10.1016/S0021-9258(18)42471-4 . 1569099 . free .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Research . 6 . 9 . 791–806 . September 1996 . 8889548 . 10.1101/gr.6.9.791 . free .
• Dittmar KD, Pratt WB . Folding of the glucocorticoid receptor by the reconstituted Hsp90-based chaperone machinery. The initial hsp90.p60.hsp70-dependent step is sufficient for creating the steroid binding conformation . The Journal of Biological Chemistry . 272 . 20 . 13047–54 . May 1997 . 9148915 . 10.1074/jbc.272.20.13047 . free .
• Dittmar KD, Demady DR, Stancato LF, Krishna P, Pratt WB . Folding of the glucocorticoid receptor by the heat shock protein (hsp) 90-based chaperone machinery. The role of p23 is to stabilize receptor.hsp90 heterocomplexes formed by hsp90.p60.hsp70 . The Journal of Biological Chemistry . 272 . 34 . 21213–20 . August 1997 . 9261129 . 10.1074/jbc.272.34.21213 . free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Zou J, Guo Y, Guettouche T, Smith DF, Voellmy R . Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1 . Cell . 94 . 4 . 471–80 . August 1998 . 9727490 . 10.1016/S0092-8674(00)81588-3 . 9234420 . free .
• Scanlan MJ, Gordan JD, Williamson B, Stockert E, Bander NH, Jongeneel V, Gure AO, Jäger D, Jäger E, Knuth A, Chen YT, Old LJ . Antigens recognized by autologous antibody in patients with renal-cell carcinoma . International Journal of Cancer . 83 . 4 . 456–64 . November 1999 . 10508479 . 10.1002/(SICI)1097-0215(19991112)83:4<456::AID-IJC4>3.0.CO;2-5 . 21839750 .
• Scheufler C, Brinker A, Bourenkov G, Pegoraro S, Moroder L, Bartunik H, Hartl FU, Moarefi I . Structure of TPR domain-peptide complexes: critical elements in the assembly of the Hsp70-Hsp90 multichaperone machine . Cell . 101 . 2 . 199–210 . April 2000 . 10786835 . 10.1016/S0092-8674(00)80830-2 . 18200460 . free .
• Hernández MP, Chadli A, Toft DO . HSP40 binding is the first step in the HSP90 chaperoning pathway for the progesterone receptor . The Journal of Biological Chemistry . 277 . 14 . 11873–81 . April 2002 . 11809754 . 10.1074/jbc.M111445200 . free .
• Brinker A, Scheufler C, Von Der Mulbe F, Fleckenstein B, Herrmann C, Jung G, Moarefi I, Hartl FU . Ligand discrimination by TPR domains. Relevance and selectivity of EEVD-recognition in Hsp70 x Hop x Hsp90 complexes . The Journal of Biological Chemistry . 277 . 22 . 19265–75 . May 2002 . 11877417 . 10.1074/jbc.M109002200 . free .
• Zanata SM, Lopes MH, Mercadante AF, Hajj GN, Chiarini LB, Nomizo R, Freitas AR, Cabral AL, Lee KS, Juliano MA, de Oliveira E, Jachieri SG, Burlingame A, Huang L, Linden R, Brentani RR, Martins VR . Stress-inducible protein 1 is a cell surface ligand for cellular prion that triggers neuroprotection . The EMBO Journal . 21 . 13 . 3307–16 . July 2002 . 12093732 . 125391 . 10.1093/emboj/cdf325 .
• Hernández MP, Sullivan WP, Toft DO . The assembly and intermolecular properties of the hsp70-Hop-hsp90 molecular chaperone complex . The Journal of Biological Chemistry . 277 . 41 . 38294–304 . October 2002 . 12161444 . 10.1074/jbc.M206566200 . free .
• Abbas-Terki T, Briand PA, Donzé O, Picard D . The Hsp90 co-chaperones Cdc37 and Sti1 interact physically and genetically . Biological Chemistry . 383 . 9 . 1335–42 . September 2002 . 12437126 . 10.1515/BC.2002.152 . 9277739 .
• Imai Y, Soda M, Murakami T, Shoji M, Abe K, Takahashi R . A product of the human gene adjacent to parkin is a component of Lewy bodies and suppresses Pael receptor-induced cell death . The Journal of Biological Chemistry . 278 . 51 . 51901–10 . December 2003 . 14532270 . 10.1074/jbc.M309655200 . free .
• Longshaw VM, Chapple JP, Balda MS, Cheetham ME, Blatch GL . Nuclear translocation of the Hsp70/Hsp90 organizing protein mSTI1 is regulated by cell cycle kinases . Journal of Cell Science . 117 . Pt 5 . 701–10 . February 2004 . 14754904 . 10.1242/jcs.00905 . 11902067 .
• Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ . Immunoaffinity profiling of tyrosine phosphorylation in cancer cells . Nature Biotechnology . 23 . 1 . 94–101 . January 2005 . 15592455 . 10.1038/nbt1046 . 7200157 .

Notes and References

1. Odunuga OO, Longshaw VM, Blatch GL . Hop: more than an Hsp70/Hsp90 adaptor protein . BioEssays . 26 . 10 . 1058–68 . October 2004 . 15382137 . 10.1002/bies.20107 . 45168091 .
2. Scheufler C, Brinker A, Bourenkov G, Pegoraro S, Moroder L, Bartunik H, Hartl FU, Moarefi I . Structure of TPR domain-peptide complexes: critical elements in the assembly of the Hsp70-Hsp90 multichaperone machine . Cell . 101 . 2 . 199–210 . April 2000 . 10786835 . 10.1016/S0092-8674(00)80830-2 . 18200460 . free .
3. Schmid AB et al. . 2012 . The architecture of functional modules in the Hsp90 co-chaperone Sti1/Hop . EMBO J . 31 . 6. 1506–17 . 10.1038/emboj.2011.472. 3321170 . 22227520.
4. Yamamoto S et al. . 2014 . ATPase activity and ATP-dependent conformational change in the co-chaperone HSP70/HSP90-organizing protein (HOP) . J. Biol. Chem. . 289 . 14. 9880–6 . 10.1074/jbc.m114.553255. 3975032 . 24535459. free .
5. Martins VR, Graner E, Garcia-Abreu J, de Souza SJ, Mercadante AF, Veiga SS, Zanata SM, Neto VM, Brentani RR . Complementary hydropathy identifies a cellular prion protein receptor . Nature Medicine . 3 . 12 . 1376–82 . December 1997 . 9396608 . 10.1038/nm1297-1376 . 20605773 .
6. Zanata SM, Lopes MH, Mercadante AF, Hajj GN, Chiarini LB, Nomizo R, Freitas AR, Cabral AL, Lee KS, Juliano MA, de Oliveira E, Jachieri SG, Burlingame A, Huang L, Linden R, Brentani RR, Martins VR . Stress-inducible protein 1 is a cell surface ligand for cellular prion that triggers neuroprotection . The EMBO Journal . 21 . 13 . 3307–16 . July 2002 . 12093732 . 125391 . 10.1093/emboj/cdf325 .
7. Iwasaki S, Sasaki HM, Sakaguchi Y, Suzuki T, Tadakuma H, Tomari Y . Defining fundamental steps in the assembly of the Drosophila RNAi enzyme complex . Nature . 521 . 7553 . 533–6 . May 2015 . 25822791 . 10.1038/nature14254 . 2015Natur.521..533I . 4450303 .
8. Gangaraju VK, Yin H, Weiner MM, Wang J, Huang XA, Lin H . Drosophila Piwi functions in Hsp90-mediated suppression of phenotypic variation . Nature Genetics . 43 . 2 . 153–8 . February 2011 . 21186352 . 10.1038/ng.743 . 3443399.
9. Karam JA, Parikh RY, Nayak D, Rosenkranz D, Gangaraju VK . Co-chaperone Hsp70/Hsp90-organizing protein (Hop) is required for transposon silencing and Piwi-interacting RNA (piRNA) biogenesis . The Journal of Biological Chemistry . 292 . 15 . 6039–6046 . April 2017 . 28193840 . 10.1074/jbc.C117.777730 . 5391737. free .
10. Zanata SM, Lopes MH, Mercadante AF, Hajj GN, Chiarini LB, Nomizo R, Freitas AR, Cabral AL, Lee KS, Juliano MA, de Oliveira E, Jachieri SG, Burlingame A, Huang L, Linden R, Brentani RR, Martins VR . Stress-inducible protein 1 is a cell surface ligand for cellular prion that triggers neuroprotection . The EMBO Journal . 21 . 13 . 3307–16 . July 2002 . 12093732 . 125391 . 10.1093/emboj/cdf325 .
11. Scheufler C, Brinker A, Bourenkov G, Pegoraro S, Moroder L, Bartunik H, Hartl FU, Moarefi I . Structure of TPR domain-peptide complexes: critical elements in the assembly of the Hsp70-Hsp90 multichaperone machine . Cell . 101 . 2 . 199–210 . April 2000 . 10786835 . 10.1016/S0092-8674(00)80830-2 . 18200460 . free .
12. Johnson BD, Schumacher RJ, Ross ED, Toft DO . Hop modulates Hsp70/Hsp90 interactions in protein folding . The Journal of Biological Chemistry . 273 . 6 . 3679–86 . February 1998 . 9452498 . 10.1074/jbc.273.6.3679 . free .