Polypeptide that interacts with heat shock proteins

An isolated polypeptide which induces ubiquitylation of a heat shock bound substrate.

An isolated polypeptide comprising an amino acid sequence having greater than about 40% sequence identity to at least one of SEQ ID NOs:

• 2, 7, and 8.

An isolated polypeptide comprising an amino acid sequence represented by at least one of SEQ ID NOs:

• 2, 7, and 8.

A polypeptide comprising amino acid sequence represented by at least one of SEQ ID NOs:

• 2, 7, and 8 wherein the polypeptide has a molecular weight as determined by SDS polyacrylamide gel electrophoresis of about 30 kD to about 40 kD.

A polypeptide that negatively regulates binding of a heat shock protein to a substrate wherein a nucleic acid encoding the polypeptide hybridizes to a nucleic acid or a nucleic acid complement of at least one of SEQ ID NOs:

• 1, 9, 10, and 11 under hybridization conditions of 0.015 M NaCl/0.0015 M sodium citrate (SSC) and about 0.1% sodium dodecyl sulfate (SDS) at about 50° C. to about 65° C.

A polypeptide that induces ubiquitylation of a heat shock bound substrate wherein a nucleic acid encoding the polypeptide hybridizes to a nucleic acid or a nucleic acid complement of at least one of SEQ ID NOs:

• 1, 9, 10, and 11 under hybridization conditions of 0.015 M NaCl/0.0015 M sodium citrate (SSC) and about 0.1% sodium dodecyl sulfate (SDS) at about 50° C. to about 65° C.

A polypeptide that negatively regulates binding of a heat shock protein to a substrate and induces ubiquitylation of a heat shock bound substrate wherein a nucleic acid encoding the polypeptide hybridizes to a nucleic acid or a nucleic acid complement of at least one of SEQ ID NOs:

• 1, 9, 10, and 11 under hybridization conditions of 0.015 M NaCl/0.0015 M sodium citrate (SSC) and about 0.1% sodium dodecyl sulfate (SDS) at about 50° C. to about 65° C.

A nucleic acid fragment capable of hybridizing to at least one of SEQ ID NOs:

• 1, 9, 10, and 11, or a complement of at least one of SEQ ID NOs:
• 1, 9, 10, and 11, under hybridization conditions of 0.015 M NaCl/0.0015 M sodium citrate (SSC) and about 0.1% sodium dodecyl sulfate (SDS) at about 50° C. to about 65° C.

An isolated nucleic acid fragment comprising a nucleic acid sequence represented by at least one of SEQ ID NOs:

• 1, 9, 10, and 11, or a complement thereof.

A nucleic acid fragment having a nucleic acid sequence with at least about 60% nucleic acid identity to at least one of SEQ ID NOs:

• 1, 9, 10, and 11, or a complement of the nucleic acid fragment.

A method for identifying an inhibitor of a polypeptide that has negative regulating activity for a heat shock protein bound to a substrate, the method comprising incubating the polypeptide with a compound under conditions that promote the negative regulating activity of the polypeptide when the compound is not present and determining if the negative regulating activity of the polypeptide is reduced relative to the negative regulating activity of the polypeptide in the absence of the compound.

A method for identifying an inhibitor of a polypeptide that induces ubiquitylation of a heat shock bound substrate, the method comprising incubating the polypeptide with a compound under conditions that promote the ubiquitylation activity of the polypeptide when the compound is not present and determining if the ubiquitylation activity of the polypeptide is reduced relative to the ubiquitylation activity of the polypeptide in the absence of the compound.

A method for identifying an inhibitor of a polypeptide that has negative regulating activity for a heat shock protein bound to a substrate and induces ubiquitylation of a heat shock bound substrate, the method comprising incubating the polypeptide with a compound under conditions that promote the ubiquitylation activity of the polypeptide when the compound is not present and determining if the ubiquitylation activity of the polypeptide is reduced relative to the ubiquitylation activity of the polypeptide in the absence of the compound.

A method of expressing a nucleic acid fragment that encodes a polypeptide, the presence of which is associated with a negative regulation of a heat shock protein, the method comprising expressing the nucleic acid fragment in a cultured host cell transformed with an expression vector comprising the nucleic acid fragment operably linked to control sequences recognized by the host cell.

A method of expressing a nucleic acid fragment that encodes a polypeptide, the presence of which is associated with ubiquitylation of a heat shock bound substrate, the method comprising expressing the nucleic acid fragment in a cultured host cell transformed with an expression vector comprising the nucleic acid fragment operably linked to control sequences recognized by the host cell.

A method of expressing a nucleic acid fragment that encodes a polypeptide, the presence of which is associated with a negative regulation of a heat shock protein and ubiquitylation of a heat shock bound substrate, the method comprising expressing the nucleic acid fragment in a cultured host cell transformed with an expression vector comprising the nucleic acid fragment operably linked to control sequences recognized by the host cell.

A method for inhibiting a polypeptide that negatively regulates binding of a heat shock protein to a substrate in a mammal comprising administering to the mammal a composition comprising an amount of an inhibitor to an isolated polypeptide having an amino acid sequence identity of greater than about 40% to that of at least one of SEQ ID NOs:

• 2, 7, and 8.

A method for inhibiting a polypeptide that induces ubiquitylation of a heat shock bound substrate in a mammal comprising administering to the mammal a composition comprising an amount of an inhibitor to an isolated polypeptide having an amino acid sequence identity of greater than about 40% to that of at least one of SEQ ID NOs:

• 2, 7, and 8.

A method for inhibiting a polypeptide that negatively regulates binding of a heat shock protein to a substrate and induces ubiquitylation of a heat shock bound substrate in a mammal comprising administering to the mammal a composition comprising an amount of an inhibitor to an isolated polypeptide having an amino acid sequence identity of greater than about 40% to that of at least one of SEQ ID NOs:

• 2, 7, and 8.

A method for inhibiting a nucleic acid that encodes a polypeptide that negatively regulates binding of a heat shock protein to a substrate in a mammal comprising administering to the mammal a composition comprising an amount of an inhibitor to an isolated nucleic acid fragment having a nucleic acid sequence with at least about 60% nucleic acid identity to that of at least one of SEQ ID NOs:

• 1, 9, 10, and 11, or a complement of the nucleic acid fragment.

A method for inhibiting a nucleic acid that encodes a polypeptide that induces ubiquitylation of a heat shock bound substrate in a mammal comprising administering to the mammal a composition comprising an amount of an inhibitor to an isolated nucleic acid fragment having a nucleic acid sequence with at least about 60% nucleic acid identity to that of at least one of SEQ ID NOs:

• 1, 9, 10, and 11, or a complement of the nucleic acid fragment.