Uncoating protein (hsc70) binds a conformationally labile domain of clathrin light chain LCa to stimulate ATP hydrolysis

DeLuca-Flaherty, Camille; McKay, David; Parham, Peter; Hill, Beth

doi:10.1016/0092-8674(90)90263-e

Cited by 152 publications

(93 citation statements)

References 42 publications

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“…This protein was found to be multifunctional. It functions as clathrin uncoating ATPase (Chappell et al, 1986;Deluca-Flaherty et al, 1990) and as molecular chaperone that binds to nascent polypeptides and maintains them in unfolded states, to facilitate their intracellular translocation (Deshaies et al, 1988;Chirico et al, 1988) and/or to accelerate their proper folding and oligomerisation (Beckmann et al, 1990;Pelham, 1990). Recently, HSP72 has been shown to be involved the in vivo assembly of microtubules (Gupta, 1990).…”

Section: Discussionmentioning

confidence: 99%

Induction of HSP70 is associated with vincristine resistance in heat-shocked 9L rat brain tumour cells

Lee¹,

Lin²,

Chen³

et al. 1992

Br J Cancer

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SummaryThe most prominent cellular changes in heat-shock response are induction of HSPs synthesis and reorganisation of cytoskeleton. Vincristine was used as a tool to evaluate the integrity of microtubules in 9L rat brain tumour cells recovering from heat-shock treatment. Cells treated at 45°C for 15 min and recovered under normal growing condition became resistant to vincristine-inflicted cytotoxicity and microtubule destruction. Among all HSPs, the level of HSP70 and the degree of vincristine resistance are best correlated. HSP70and tubulin were found to be associated with each other as they were co-immunoprecipitated by either anti-HSP70 or anti-p-tubulin monoclonal antibody. The current studies establish for the first time that HSP70can complex with tubulin in cells and this association may stabilise the organisation of microtubules thus protect the heat-treated cells from vincristine damage. These findings are noteworthy in combining hyperthermia and chemotherapy in the management of malignant diseases.Heat-shock proteins (HSPs) are a small set of proteins induced in cells subjected to supraoptimal temperature and other related physiological stresses (Lindquist & Craig, 1988;Schlesinger, 1990;Schlesinger et al., 1990; Morimoto et al., 1990). The synthesis of HSPs is suggested to be related to the development of thermotolerance in cells that survived the initial heat-treatment (Li & Mak, 1985;Hahn & Li, 1990;Black & Subjeck, 1990). The HSPs are highly conservative and usually termed by their apparent molecular weights. Three classes of major HSPs, i.e., HSPl10, 90 and 70 are commonly detected in mammalian cells (Lindquist & Craig, 1988). HSP70 exists as a family in most organisms and has been the most extensively studied. In rodent cells, this family consists of two closely related proteins (>80% homology at the amino acid level) which have been known as the constitutive form of HSP70 (also known as HSC70, designated as HSP72 hereafter because of its slightly higher molecular weight) and the inducible form of HSP70 (designated as the HSP70 hereafter) (Hightower & White, 1981;Lee et al., 1991). HSP72 is slightly heat inducible, constitutively expressed and found at higher levels in growing cells than in resting cells (Pelham, 1986). This protein was found to be multifunctional. It functions as clathrin uncoating ATPase (Chappell et al., 1986;Deluca-Flaherty et al., 1990) and as molecular chaperone that binds to nascent polypeptides and maintains them in unfolded states, to facilitate their intracellular translocation (Deshaies et al., 1988;Chirico et al., 1988) and/or to accelerate their proper folding and oligomerisation (Beckmann et al., 1990;Pelham, 1990). Recently, HSP72 has been shown to be involved the in vivo assembly of microtubules (Gupta, 1990). On the other hand, HSP70 is highly heat inducible and hardly detectable under normal conditions. Its function is suggested to be similar to that of HSP72 because of the high degree of homology between these two proteins (Lindquist & Craig, 1988). In additi...

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Section: Discussionmentioning

confidence: 99%

Induction of HSP70 is associated with vincristine resistance in heat-shocked 9L rat brain tumour cells

Lee¹,

Lin²,

Chen³

et al. 1992

Br J Cancer

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“…If the uncoating ATPase has a role in vivo the question remains as to how it distinguishes between coated vesicles and coated pits which have not yet pinched off. In a recent study (DeLuca-Flaherty et al, 1990) it was demonstrated that purified light chains can bind to uncoating ATPase thus stimulating ATP hydrolysis and that LCa has a greater stimulatory effect than LCP. In addition, purified LCa is capable of inhibiting the uncoating process.…”

Section: Uncout Ingmentioning

confidence: 99%

“…The interaction of LCa with uncoating ATPase has been localised to residues 47-71 of LCa and this region undergoes conformational changes which affect its binding to uncoating ATPase in response to changes in ionic strength and calcium concentration. DeLuca-Flaherty et al (1990) propose that since coated vesicles, unlike coated pits, can change the ionic state of their lumen, that changes in ionic fluxes across a coated vesicle membrane induce a conformational change in the light chain such that it can bind to uncoating ATPase and so trigger uncoating. However, since empty coats and Triton-extracted coated vesicles are equally good substrates for the uncoating ATPase, the difference may lie in the energy states of the lattice at different stages of invagination.…”

Section: Uncout Ingmentioning

confidence: 99%

The mechanism of receptor‐mediated endocytosis

Smythe

Warren

1991

European Journal of Biochemistry

153

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“…Research during the last decade has revealed a group of proteins called co-chaperones, which are involved in the control of ATPase activity of Hsp70, thereby modifying its affinity for protein substrates (3,6,7). One of these proteins, Hsp70-binding protein I (HspBP1), was initially identified as an Hsp70-binding protein inhibiting its chaperone activity and was shown to bind to the ATP domain of Hps70 and inhibit its ATPase activity (8).…”

mentioning

confidence: 99%

“…The main function of these proteins is to protect cells against damage produced by various stress factors (1). Hsp70 is an ATP-dependent chaperone, which promotes folding of nascent proteins or refolding of the proteins that were partially denatured after exposure of cells in an unfavorable environment (1)(2)(3). In addition, Hsp70 is involved in assembly of multiprotein complexes and protein translocation across the plasma membrane (4).…”

mentioning

confidence: 99%

The Heat Shock-binding Protein (HspBP1) Protects Cells against the Cytotoxic Action of the Tag7-Hsp70 Complex

Yashin

Dukhanina

Kabanova

et al. 2011

Journal of Biological Chemistry

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Heat shock-binding protein HspBP1 is a member of the Hsp70 co-chaperone family. The interaction between HspBP1 and the ATPase domain of the major heat shock protein Hsp70 up-regulates nucleotide exchange and reduces the affinity between Hsp70 and the peptide in its peptide-binding site. Previously we have shown that Tag7 (also known as peptidoglycan recognition protein PGRP-S), an innate immunity protein, interacts with Hsp70 to form a stable Tag7-Hsp70 complex with cytotoxic activity against some tumor cell lines. This complex can be produced in cytotoxic lymphocytes and released during interaction with tumor cells. Here the effect of HspBP1 on the cytotoxic activity of the Tag7-Hsp70 complex was examined. HspBP1 could bind not only to Hsp70, but also to Tag7. This interaction eliminated the cytotoxic activity of Tag7-Hsp70 complex and decreased the ATP concentration required to dissociate Tag7 from the peptide-binding site of Hsp70. Moreover, HspBP1 inhibited the cytotoxic activity of the Tag7-Hsp70 complex secreted by lymphocytes. HspBP1 was detected in cytotoxic CD8؉ lymphocytes. This protein was released simultaneously with Tag7-Hsp70 during interaction of these lymphocytes with tumor cells. The simultaneous secretion of the cytotoxic complex with its inhibitor could be a mechanism protecting normal cells from the cytotoxic effect of this complex.

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Uncoating protein (hsc70) binds a conformationally labile domain of clathrin light chain LCa to stimulate ATP hydrolysis

Cited by 152 publications

References 42 publications

Induction of HSP70 is associated with vincristine resistance in heat-shocked 9L rat brain tumour cells

Induction of HSP70 is associated with vincristine resistance in heat-shocked 9L rat brain tumour cells

The mechanism of receptor‐mediated endocytosis

The Heat Shock-binding Protein (HspBP1) Protects Cells against the Cytotoxic Action of the Tag7-Hsp70 Complex

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