In Vivo Analysis of the Hsp90 Cochaperone Sti1 (p60)

Chang, Hui; Nathan, Debra F.; Lindquist, Susan

doi:10.1128/mcb.17.1.318

Cited by 210 publications

(217 citation statements)

References 57 publications

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Section: Introductionmentioning

confidence: 99%

“…Whether the cochaperones are required for this reaction is not clear, because purified Hsp70 and Hsp90 can together facilitate folding of GR in vitro, whereas cochaperones such as Hop stimulate the reaction (Morishima et al, 2000;Rajapandi et al, 2000). Furthermore, deletion of yeast Hop (STI1), or p23 (SBA1) does not result in a slow growth phenotype except under stress conditions (Nicolet and Craig, 1989;Chang et al, 1997;Bohen, 1998;Fang et al, 1998).Another question is whether the scheme described above for nuclear receptors reflects a set of general principles by which Hsp90 functions and whether it applies to other client types. Folding of protein kinases, for example, requires a cochaperone called Cdc37, that does not associate with GR or PR, although it does function in activation of androgen receptor and a viral reverse transcriptase (Fliss et al, 1997;Rao et al, 2001;Wang et al, 2002).…”

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confidence: 99%

“…Levels of FIG1 and HHF1 mRNA were determined by quantitative real-time rtPCR relative to ARP5, whose mRNA levels do not change upon pheromone treatment (Roberts et al, 2000; our unpublished results). The cochaperones chosen for study have all been characterized previously as Hsp90 binding proteins, and include Cpr6, Cpr7, Hch1, Sba1, Sse1, and Sti1 (Duina et al, 1996;Chang et al, 1997;Bohen, 1998;Fang et al, 1998;Liu et al, 1999;Panaretou et al, 2002;Lotz et al, 2003). Ydj1, a cochaperone of Hsp70 was also included because it affects the activity of Hsp90 clients (Bohen et al, 1995).…”

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confidence: 99%

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Sti1 and Cdc37 Can Stabilize Hsp90 in Chaperone Complexes with a Protein Kinase

Lee

Shabbir

Cardozo

et al. 2004

MBoC

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Hsp90 functions in association with several cochaperones for folding of protein kinases and transcription factors, although the relative contribution of each to the overall reaction is unknown. We assayed the role of nine different cochaperones in the activation of Ste11, a Saccharomyces cerevisiae mitogen-activated protein kinase kinase kinase. Studies on signaling via this protein kinase pathway was measured by ␣-factor-stimulated induction of FIG1 or lacZ, and repression of HHF1. Several cochaperone mutants tested had reduced FIG1 induction or HHF1 repression, although to differing extents. The greatest defects were in cpr7⌬, sse1⌬, and ydj1⌬ mutants. Assays of Ste11 kinase activity revealed a pattern of defects in the cochaperone mutant strains that were similar to the gene expression studies. Overexpression of CDC37, a chaperone required for protein kinase folding, suppressed defects the sti1⌬ mutant back to wild-type levels. CDC37 overexpression also restored stable Hsp90 binding to the Ste11 protein kinase domain in the sti1⌬ mutant strain. These data suggest that Cdc37 and Sti1 have functional overlap in stabilizing Hsp90:client complexes. Finally, we show that Cns1 functions in MAP kinase signaling in association with Cpr7. INTRODUCTIONAmong several major classes of molecular chaperone that have been characterized, Hsp90 appears to function primarily in folding of signal transducing proteins such as transcription factors and protein kinases (Caplan, 1999;Prodromou and Pearl, 2003). Hsp90 does not act alone in this capacity, but in association with several cochaperones that may also have chaperone function as defined by their ability to prevent polypeptide aggregation in vitro.The current understanding of how Hsp90 cochaperones function derived from in vitro studies on progesterone receptors (PR) and glucocorticoid receptors (GR; Toft, 1997, 2003). The results of these studies showed that Hsp70 and Hsp40 first interact with the receptor ligandbinding domain. Hsp90 is recruited into this complex by the cochaperone called Hop, which interacts with both Hsp90 and Hsp70. Subsequently, Hsp70 and Hop are displaced by other cochaperones, such as one of many immunophilins and p23. Folding occurs in association with ATP hydrolysis by Hsp90, which is stimulated by another cochaperone called Aha1 (and its paralog Hch1; Panaretou et al., 2002;Lotz et al., 2003). It is unclear whether folding occurs while the receptor is in association with Hsp90 or after its release. Whether the cochaperones are required for this reaction is not clear, because purified Hsp70 and Hsp90 can together facilitate folding of GR in vitro, whereas cochaperones such as Hop stimulate the reaction (Morishima et al., 2000;Rajapandi et al., 2000). Furthermore, deletion of yeast Hop (STI1), or p23 (SBA1) does not result in a slow growth phenotype except under stress conditions (Nicolet and Craig, 1989;Chang et al., 1997;Bohen, 1998;Fang et al., 1998).Another question is whether the scheme described above for nuclear receptors reflects a set of ...

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Sti1 and Cdc37 Can Stabilize Hsp90 in Chaperone Complexes with a Protein Kinase

Lee

Shabbir

Cardozo

et al. 2004

MBoC

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“…Its interaction with regulatory factors is a prerequisite for such factors to interact properly with ligands and target molecules. In addition to the typically dimeric Hsp90, the functional complexes usually include other heat shock proteins and associated factors (Chang et al, 1997;. The impact of Hsp90 on the morphological differentiation of multicellular organisms was demonstrated recently, and a role as molecular capacitor of morphological evolution has been proposed (Rutherford and Lindquist, 1998;Lele et al, 1999).…”

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confidence: 99%

Heat Shock Protein 90 Homeostasis Controls Stage Differentiation in Leishmania donovani

Wiesgigl

Clos

2001

MBoC

186

177

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The differentiation of Leishmania parasites from the insect stage, the promastigote, toward the pathogenic mammalian stage, the amastigote, is triggered primarily by the rise in ambient temperature encountered during the insect-to-mammal transmission. We show here that inactivation of heat shock protein (Hsp) 90, with the use of the drugs geldanamycin or radicicol, mimics transmission and induces the differentiation from the promastigote to the amastigote stage. Geldanamycin also induces a growth arrest of cultured promastigotes that can be forestalled by overexpression of the cytoplasmic Hsp90. Moreover, we demonstrate that Hsp90 serves as a feedback inhibitor of the cellular heat shock response in Leishmania. Our results are consistent with Hsp90 homeostasis serving as cellular thermometer for these primitive eukaryotes, controlling both the heat shock response and morphological differentiation. INTRODUCTIONProtozoan parasites of the genus Leishmania are transmitted by blood-feeding sand flies to mammalian hosts, including humans, whereby they encounter a rise in ambient temperature. Subjecting cultured insect stages, the promastigotes, of various Leishmania species to a similar temperature upshift in vitro results in the transient posttranscriptional upregulation of both heat shock protein (Hsp) 90 (also known as Hsp83) and Hsp70 synthesis and a persistent induction of Hsp100 expression Brandau et al., 1995;Krobitsch et al., 1998). Moreover, species such as L. mexicana, L. pifanoi, and L. donovani will, during heat stress and acidification of the medium, show a morphological transition toward the mammalian stage, the amastigote (Zilberstein and Shapira, 1994;Saar et al., 1998). Such axenic amastigotes are indistinguishable from true host tissue-derived intracellular amastigotes (Bates, 1993;Pan et al., 1993;Charest and Matlashewski, 1994;Charest et al., 1996;Gupta et al., 1996;Saar et al., 1998). Thus, the rise of temperature encountered during transmission can be viewed not as stress but rather as signal for cellular differentiation.We have shown previously that Hsp100 is critical for the expression of some amastigote stage-specific proteins and for overall virulence of the parasites (Hubel et al., 1997;Krobitsch et al., 1998); however, gene replacement mutants lacking Hsp100 still show, induced by elevated temperature, morphological differentiation to viable amastigote-like culture stages, indicating that the induction of morphological differentiation occurs independently or upstream of Hsp100 (Krobitsch et al., 1998;Krobitsch and Clos, 1999).Another chaperone, Hsp90 (Hsp83), is one of the most abundant proteins in Leishmania, constituting 2.8% of the cellular protein . Hsp90 (Hsp83) is encoded by multiple gene copies and is found in the soluble fraction of the cytoplasm (Shapira and Pinelli, 1989;Brandau et al., 1995;Hubel and Clos, 1996). Its sequence is distinct from the Grp94 homologue of L. infantum, which was characterized recently (Larreta et al., 2000). In higher eukaryotes and in yeast, cytosolic H...

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“…Hop is an indispensable component of a dynamic heterocomplex chaperoning machine that is involved in the functional maturation of a number of unrelated protein substrates [2][3][4]. The earliest detectable components of this heterocomplex include hsp70, hsp40 and the hsp70-interacting protein (Hip).…”

Section: Introductionmentioning

confidence: 99%

Heat shock cognate protein 70 chaperone-binding site in the co-chaperone murine stress-inducible protein 1 maps to within three consecutive tetratricopeptide repeat motifs

et al. 2000

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Murine stress-inducible protein 1 (mSTI1) is a co-chaperone homologous with the human heat shock cognate protein 70 (hsc70)\heat shock protein 90 (hsp90)-organizing protein (Hop). The concomitant interaction of mSTI1 with hsp70 and hsp90 at its N-and C-termini respectively is mediated by the tetratricopeptide repeat (TPR) motifs in these regions. With the use of co-precipitation assays, we show here that the N-terminal TPR domain of mSTI1 without extensive flanking regions is both necessary and sufficient to mediate a specific interaction with hsc70. In contrast, other TPR-containing co-chaperones require TPR flanking regions for target substrate recognition, suggesting different mechanisms of TPR-mediated chaperone-co-chaperone interactions. Furthermore, the interaction between mSTI1 and hsc70 was analysed to ascertain the effect of replacing or deleting conserved amino acid residues and sequences within the three

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In Vivo Analysis of the Hsp90 Cochaperone Sti1 (p60)

Cited by 210 publications

References 57 publications

Sti1 and Cdc37 Can Stabilize Hsp90 in Chaperone Complexes with a Protein Kinase

Sti1 and Cdc37 Can Stabilize Hsp90 in Chaperone Complexes with a Protein Kinase

Heat Shock Protein 90 Homeostasis Controls Stage Differentiation in Leishmania donovani

Heat shock cognate protein 70 chaperone-binding site in the co-chaperone murine stress-inducible protein 1 maps to within three consecutive tetratricopeptide repeat motifs

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