# US 2013/0157959 A1 · Use of hades as tumor suppressor target

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- Number: US 2013/0157959 A1
- Document ID: US20130157959A1
- Status: Published application
- Kind: A1
- Application number: 13/641,910
- Filed: 2011-04-21
- Published: 2013-06-20
- Earliest claimed: 2010-04-21
- Assignees: Konkuk University Industrial Cooperation Corp.
- Inventors: Sungkwan An; Jin Hyuk Jung; Jae Ho Lee; Seunghee Bae
- Web page: https://patentgrep.com/patent/US20130157959A1

## CPC

- A61K 38/17: from animals; from humans {(enzyme inhibitors A61K38/005)}
- A61K 38/53: Ligases (6)
- A61P 35/00: Antineoplastic agents
- C07K 16/18: against material from animals or humans
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

The present invention relates to a new use of Hades as a tumor suppressor target, more particularly to a composition for suppressing tumor comprising an expression or action inhibitor of Hades protein having an amino acid sequence of SEQ ID NO: 2 as an effective ingredient. The present inventors have found that the overexpressed Hades protein interacts with p53 to inhibit the exonuclear mechanism of p53 and the knowdown of Hades induces increase in the expression of p53, demonstrating that Hades is a negative regulator to p53. Therefore, it would be understood that the inhibition of Hades overexpressed in tumor cells contributes to tumor-supressive effects of p53. The drug candidates capable of modulating the expression of the Hades protein, inhibiting the actions of the Hades protein or inhibiting interecation between Hades and p53 are considered a promising anticancer drug.

## Claims

### Claim 1

A composition for suppressing tumor comprising an expression or action inhibitor of Hades protein having an amino acid sequence of SEQ ID NO: 2 as an effective ingredient.

### Claim 2 (depends on 1)

The composition for suppressing tumor according to claim 1, wherein the Hades is over-expressed in tumor cells.

### Claim 3 (depends on 1)

The composition for suppressing tumor according to claim 1, wherein the expression or action inhibitor of Hades protein downregulates the transcription or translation of Hades gene or inhibits the action of Hades protein.

### Claim 4 (depends on 1)

The composition for suppressing tumor according to claim 1, wherein the expression inhibitor of Hades protein is Hades siRNA (short interfering RNA) having a base sequence of SEQ ID NO: 4 or 5, or a gene transcribing the Hades siRNA.

### Claim 5 (depends on 1)

The composition for suppressing tumor according to claim 1, wherein the action inhibitor of Hades protein is a substance inhibiting the interaction between Hades and p53.

### Claim 6 (depends on 5)

The composition for suppressing tumor according to claim 5, wherein the interaction between Hades and p53 inhibits DNA binding of p53, transcription activity, stress-induced apoptosis and p53-induced apoptosis.

### Claim 7 (depends on 5)

The composition for suppressing tumor according to claim 5, wherein the interaction betweem Hades and p53 induces ubiquitination of p53.

### Claim 8 (depends on 1)

The composition for suppressing tumor according to claim 1, wherein the action inhibitor of Hades protein targets a RNIG-finger domain at the C-terminus of Hades.

### Claim 9

A method for screening anti-cancer agent comprising:
(a) treating an agent in animal cells expressing Hades protein; and
(b) determining whether the expression of Hades protein decreases as compared to a control group in which the animal cells are not treated with the agent.

### Claim 10

A method for screening anti-cancer agent comprising:
(a) contacting Hades protein comprising p53-binding site or its fragment and p53 in the existance of an agent; and
(b) determining whether the interaction between Hades and p53 is inhibited as compared to a control group in which the agent does not exist.

### Claim 11 (depends on 10)

The Method for screening anti-cancer agent according to claim 10, wherein the fragment of Hades comprises p53-binding site (RING-finger domain at the C-terminus) having an amino acid sequence of SEQ ID NO: 3.

### Claim 12 (depends on 10)

The Method for screening anti-cancer agent according to claim 10, wherein the interaction between Hades and p53 occures between p53-binding site (RING-finger domain at the C-terminus)of Hades and DNA-bindg domain of p53.

### Claim 13 (depends on 10)

The Method for screening anti-cancer agent according to claim 10, wherein the interaction between Hades and p53 at the (b) step is detected by immunoprecipitation assay, GST pull-down assay and colony-formation assay.

### Claim 14 (depends on 9)

An anti-cancer composition comprising the agent screened by the method for screening anti-cancer agent according to claim 9 as an effective ingredient.

### Claim 15

A kit for screening anti-cancer agent which inhibits interaction between Hades and p53 comprising:
(a) a polypeptide comprising p53-binding site (RING-finger domain at the C-terminus)of Hades;
(a) a polypeptide comprising DNA-binding domain of p53; and
(c) an reagent for detecting the interaction between the polypeptides.

### Claim 16 (depends on 10)

An anti-cancer composition comprising the agent screened by the method for screening anti-cancer agent according to claim 10 as an effective ingredient.
