CN113289001A - Application of Vpr protein N-terminal amino acid polypeptide for regulating and controlling tumor cell apoptosis in preparation of antitumor drugs - Google Patents
Application of Vpr protein N-terminal amino acid polypeptide for regulating and controlling tumor cell apoptosis in preparation of antitumor drugs Download PDFInfo
- Publication number
- CN113289001A CN113289001A CN202011549618.5A CN202011549618A CN113289001A CN 113289001 A CN113289001 A CN 113289001A CN 202011549618 A CN202011549618 A CN 202011549618A CN 113289001 A CN113289001 A CN 113289001A
- Authority
- CN
- China
- Prior art keywords
- amino acid
- tumor cell
- vpr
- cell apoptosis
- vpr protein
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/162—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from virus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/16011—Human Immunodeficiency Virus, HIV
- C12N2740/16022—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
Abstract
The invention discloses an application of Vpr protein N-terminal amino acid polypeptide for regulating and controlling tumor cell apoptosis in preparing an anti-tumor medicament, wherein the polypeptide is derived from 23 th to 37 th amino acids at the N terminal of HIV protein Vpr. The 23 rd to 37 th amino acid sequence of the N end of the Vpr protein is SEQ ID NO. 1. 23-37 amino acids at the N end of the Vpr protein and an adenine nucleotide transporter 1 or an adenine nucleotide transporter 3 act together to promote tumor cell apoptosis; and the complex with adenine nucleotide transport carrier 2 inhibits the tumor cell apoptosis. The amino acid polypeptide sequence of the application is derived from virus self protein, and the reagent can regulate the proliferation and apoptosis of tumor cells through a new mechanism and can be used for biological treatment of tumors.
Description
Technical Field
The invention relates to the field of biotechnology, in particular to application of Vpr protein N-terminal amino acid polypeptide for regulating and controlling tumor cell apoptosis in preparing an antitumor medicament.
Background
The major role of the Human Immunodeficiency Virus (HIV) expressed viral protein r (vpr) is to regulate apoptosis through multiple pathways, leading to the progressive depletion of CD4+ T cells during HIV infection, which in turn leads to the destruction of the host immune system. The main characteristics of tumor cells are that the proliferation is active and immortalized, the inhibition of the growth of the tumor cells and the induction of apoptosis are considered as effective ways of the action of the antitumor drugs, but the current chemotherapeutic drugs have single apoptosis regulating means, are easy to generate drug resistance and have poor action specificity, so the treatment effect is not ideal.
Disclosure of Invention
The invention aims to solve the problems in the prior art, and provides application of Vpr protein N-terminal amino acid polypeptide for regulating and controlling tumor cell apoptosis in preparing an anti-tumor medicament.
The invention adopts the following technical scheme.
An application of Vpr protein N-terminal amino acid polypeptide for regulating and controlling tumor cell apoptosis in preparing antitumor drugs.
Furthermore, the polypeptide is derived from 23 th to 37 th amino acids at the N terminal of the Vpr protein of the AIDS.
Furthermore, the sequence of 23 rd to 37 th amino acids at the N end of the Vpr protein is SEQ ID NO. 1.
Furthermore, 23 th to 37 th amino acids at the N terminal of the Vpr protein and the adenine nucleotide transporter 1 or the adenine nucleotide transporter 3 work together to promote the apoptosis of tumor cells; and the complex with adenine nucleotide transport carrier 2 inhibits the tumor cell apoptosis.
The present invention obtains the following advantageous effects.
The 23 rd to 37 th amino acids at the N end of the HIV Vpr protein can regulate and control the apoptosis of tumor cells through a new mechanism, and have important significance for developing and preparing new antitumor drugs. The Vpr protein can induce apoptosis through various ways, and is an ideal candidate molecule for preparing antitumor drugs.
Drawings
FIG. 1 is a diagram showing the experimental results of the transfection of a TZM-bl cell line (cervical cancer cell strain) with the Vpr N-terminal amino acid polypeptide of the invention;
FIG. 2 is a diagram showing the results of co-transfection of the Vpr N-terminal amino acid polypeptide of the invention with ANT.
Detailed Description
The present invention will be further explained with reference to the drawings and examples.
An application of Vpr protein N-terminal amino acid polypeptide for regulating and controlling tumor cell apoptosis in preparing antitumor drugs.
The polypeptide is derived from 23 th to 37 th amino acids at the N end of the HIV Vpr protein.
The sequence of 23 rd to 37 th amino acids at the N end of the Vpr protein is EELKSEAVRHFPRIW (SEQ ID NO. 1).
23-37 amino acids at the N end of the Vpr protein and an adenine nucleotide transporter 1 or an adenine nucleotide transporter 3 act together to promote tumor cell apoptosis; and the complex with adenine nucleotide transport carrier 2 inhibits the tumor cell apoptosis.
Example 1
To study the activity and function of naturally truncated Vpr, a TZM-bl cell line (cervical cancer cell line) was transfected in parallel with wild-type Vpr-WT and truncated Vpr _54 (amino acid 54 terminated) expression vectors. As shown in figure 1, the percentage of apoptosis (Annexin-V +/PI-) of TZM-bl cells transfected with wild-type (Vpr-WT) or truncated Vpr (Vpr _54) was increased (<5% vs > 15%, P <0.05) compared to cells transfected with vector control. Furthermore, there was no significant difference in the apoptosis rate of transfected wild-type (Vpr-WT) and truncated Vpr (Vpr _54) TZM-bl cells (P > 0.05). Suggesting that truncated Vpr also has the same pro-apoptotic activity.
Example 2
To determine the specific location of a new pro-apoptotic motif at the N-terminus of the Vpr protein, a series of Vpr site-directed mutations were constructed. These mutations are nonsense mutations at amino acid positions 43, 38, 34, 30, 27 and 23 of the Vpr protein, which are subsequently transfected into TZM-bl cells. Truncated Vpr containing the complete first helical structure produced similar pro-apoptotic activity compared to transfected vector control tumor cells. These results indicate the presence of a cell death domain in the intact first helix (23aa-37aa) at the N-terminus of Vpr.
Example 3
Wild-type Vpr-WT, Vpr (71-92aa) and Vpr (71-92aa) were allowed to act on tumor cells together with adenine nucleotide transporters 1(ANT-1), ANT-3 and ANT-2, respectively. Experimental results referring to fig. 2, the experimental results showed that the N-terminal cell death domain (23-37aa) and the known C-terminal cell death domain (71-92aa) of Vpr have the same ability to promote apoptosis, and that the ability to promote apoptosis is related to the expression levels of different ANT subtypes, and that overexpression of ANT-1 and ANT-3 promotes Vpr-mediated tumor cell apoptosis, while overexpression of ANT-2 inhibits Vpr's pro-apoptotic effect.
The embodiments of the present invention are preferred embodiments of the present invention, and the scope of the present invention is not limited by these embodiments, so: all equivalent changes made according to the structure, shape and principle of the invention are covered by the protection scope of the invention.
Claims (4)
1. An application of Vpr protein N-terminal amino acid polypeptide for regulating and controlling tumor cell apoptosis in preparing antitumor drugs.
2. The use of the Vpr protein N-terminal amino acid polypeptide for modulating tumor cell apoptosis according to claim 1 in the preparation of an anti-tumor medicament, wherein: the polypeptide is derived from 23 th to 37 th amino acids at the N end of the HIV Vpr protein.
3. The use of the Vpr protein N-terminal amino acid polypeptide for modulating tumor cell apoptosis according to claim 2 in the preparation of an anti-tumor medicament, wherein: the 23 rd to 37 th amino acid sequence of the N end of the Vpr protein is SEQ ID NO. 1.
4. The use of the Vpr protein N-terminal amino acid polypeptide for regulating tumor cell apoptosis according to claim 3 in the preparation of antitumor drugs, characterized in that: 23-37 amino acids at the N end of the Vpr protein and an adenine nucleotide transporter 1 or an adenine nucleotide transporter 3 act together to promote tumor cell apoptosis; and the complex with adenine nucleotide transport carrier 2 inhibits the tumor cell apoptosis.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011549618.5A CN113289001A (en) | 2020-12-24 | 2020-12-24 | Application of Vpr protein N-terminal amino acid polypeptide for regulating and controlling tumor cell apoptosis in preparation of antitumor drugs |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011549618.5A CN113289001A (en) | 2020-12-24 | 2020-12-24 | Application of Vpr protein N-terminal amino acid polypeptide for regulating and controlling tumor cell apoptosis in preparation of antitumor drugs |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113289001A true CN113289001A (en) | 2021-08-24 |
Family
ID=77318686
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011549618.5A Pending CN113289001A (en) | 2020-12-24 | 2020-12-24 | Application of Vpr protein N-terminal amino acid polypeptide for regulating and controlling tumor cell apoptosis in preparation of antitumor drugs |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113289001A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998035032A2 (en) * | 1997-02-11 | 1998-08-13 | The Regents Of The University Of California | Methods of inducing cell cycle stasis |
| US20020068273A1 (en) * | 2000-09-11 | 2002-06-06 | Jacotot Etienne Daniel Francois | Mimetics and inhibitors of the interaction between Vpr (HIV vIral protein of regulation) and ANT (mitochondrial adenine nucleotide translocator) |
| US20030077826A1 (en) * | 2001-02-02 | 2003-04-24 | Lena Edelman | Chimeric molecules containing a module able to target specific cells and a module regulating the apoptogenic function of the permeability transition pore complex (PTPC) |
| US20040028651A1 (en) * | 2001-03-29 | 2004-02-12 | Karrupiah Muthumani | Composition and methods of using hiv vpr |
-
2020
- 2020-12-24 CN CN202011549618.5A patent/CN113289001A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998035032A2 (en) * | 1997-02-11 | 1998-08-13 | The Regents Of The University Of California | Methods of inducing cell cycle stasis |
| US20020068273A1 (en) * | 2000-09-11 | 2002-06-06 | Jacotot Etienne Daniel Francois | Mimetics and inhibitors of the interaction between Vpr (HIV vIral protein of regulation) and ANT (mitochondrial adenine nucleotide translocator) |
| US20030077826A1 (en) * | 2001-02-02 | 2003-04-24 | Lena Edelman | Chimeric molecules containing a module able to target specific cells and a module regulating the apoptogenic function of the permeability transition pore complex (PTPC) |
| US20040028651A1 (en) * | 2001-03-29 | 2004-02-12 | Karrupiah Muthumani | Composition and methods of using hiv vpr |
Non-Patent Citations (4)
| Title |
|---|
| LING DU等: "Multifactorial role of HIV-Vpr in cell apoptosis revealed by a naturally truncated 54aa variant", 《CHINESE MEDICAL JOURNAL》 * |
| 郭丽: "含有HIV-1vPr基因的重组腺病毒的制备", 《中国优秀博硕士学位论文全文数据库(硕士)医药卫生科技辑》 * |
| 魏强等: "HIV Vpr蛋白诱导细胞凋亡研究进展", 《中国生物工程杂志》 * |
| 魏强等: "人甲胎蛋白启动子控制HIV-1Vpr表达的重组腺病毒体内抑瘤效果研究", 《上海医药》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7350485B2 (en) | Compositions and methods for improving viral vector efficiency | |
| Gagat et al. | Cell-penetrating peptides and their utility in genome function modifications | |
| WO2016149484A2 (en) | Compositions and methods for specific reactivation of hiv latent reservoir | |
| KR102433761B1 (en) | ATF5 peptide variants and uses thereof | |
| KR20130019365A (en) | Protein complex for intracellular delivery and uses thereof | |
| US5573925A (en) | P53 proteins with altered tetramerization domains | |
| CN112294959A (en) | Application of C20orf112 in preparation of product for promoting cancer cell proliferation | |
| CN114592010A (en) | NK-CAR-MbIL-15 cell and preparation method and application thereof | |
| US20060099677A1 (en) | DNA/RNA transduction technology and its clinical and basic applications | |
| KR101444199B1 (en) | Cell Penetrating Peptides and Use thereof | |
| CN113289001A (en) | Application of Vpr protein N-terminal amino acid polypeptide for regulating and controlling tumor cell apoptosis in preparation of antitumor drugs | |
| KR20030062789A (en) | Biomolecule transduction peptide sim2-btm and biotechnological products including it | |
| Qi et al. | Constitutive activation of gene expression by thyroid hormone receptor results from reversal of p53-mediated repression | |
| CN110372780B (en) | Antitumor polypeptide and application thereof in antitumor field | |
| KR101444197B1 (en) | Cell Penetrating Peptides and Use thereof | |
| CN113061168B (en) | Truncated fever with thrombocytopenia syndrome virus Gn protein and application thereof | |
| CN110054678B (en) | Membrane-bound mFLT3LG protein and application thereof | |
| Yang et al. | Cell‐penetrating peptide delivery of biologically active oct4 protein into cultured Takifugu rubripes spermary cells | |
| KR101306892B1 (en) | Novel synthetic peptides improving efficiency of gene delivery and method for delivering gene using them | |
| US20060160732A1 (en) | Compositions and methods for inhibiting cell senescence and hyperproliferative disorders | |
| CN116789844A (en) | Chimeric antigen receptor of targeted CD7 protein and application thereof | |
| RU2018146446A (en) | ENVELOPE VIRUS RESISTANT TO INACTIVATION WITH COMPLETE FOR TREATMENT OF MALIGNANT TUMORS | |
| CN1240480A (en) | Methods and compositions for delivery and expression of interferon-'alpha' nucleic acids | |
| WO2007102631A1 (en) | Novel intracellular transduction peptides |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210824 |