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  Novel agent for inducing apoptosis comprising msx1 or a gene encoding the same as an active ingredientUSPTO Application #: 20070021337Title: Novel agent for inducing apoptosis comprising msx1 or a gene encoding the same as an active ingredient Abstract: The present invention relates to a novel use of Msx1 protein or a nucleotide encoding the same for inducing apoptosis. The Msx1 of the present invention induces apoptosis through direct interaction with p53 via a homeodomain and such interaction leads to increased stability, and/or nuclear localization of p53 in cells. The Msx1 or homeodomain thereof can be effectively used for the treatment of tumors, in which wild-type p53 protein has lost its function by some mechanism that inactivates p53 proteins. (end of abstract) Agent: Sheridan Ross Suite 3500 - Denver, CO, US Inventors: Je-Ho Lee, Kyoungsook Park USPTO Applicaton #: 20070021337 - Class: 514012000 (USPTO) Related Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Peptide Containing (e.g., Protein, Peptones, Fibrinogen, Etc.) Doai, Cyclopeptides, 25 Or More Peptide Repeating Units In Known Peptide Chain Structure The Patent Description & Claims data below is from USPTO Patent Application 20070021337. Brief Patent Description - Full Patent Description - Patent Application Claims
CROSS-REFERENCE TO RELATED APPLICATION [0001] This application claims priority to and the benefit of Korean Patent Application No. 10-2005-66541 filed in the Korean Industrial Property Office on Jul. 22, 2005, the contents of which are incorporated herein by reference. FIELD OF THE INVENTION [0002] The present invention relates to a novel use of Msx1 protein and nucleic acids encoding the same for modulating apoptosis. Particularly, the present invention relates to compositions for modulating apoptosis using Msx1 or nucleic acids encoding the same and use thereof in the treatment of disease states associated with abnormal apoptosis. BACKGROUND OF THE INVENTION [0003] Apoptosis, also called programmed cell death, is a form of cell death in which a series of programmed events leads to the destruction of cells (Kerr et al., British Journal of Cancer, 26: 239-257, 1972). Apoptosis plays an important role in an organism by controlling the normal development and providing a defense against many types of biological damages such as radiation, viral infections, and cancer through eliminating aged cells, unnecessary cells, and unhealthy cells, thereby leading to homeostasis of various tissues. The features of apoptosis vary among different cell types and depend upon the nature of the apoptotic stimulus, but some characteristics are common to all, that is, cell shrinkage, membrane blebbing, nuclear condensation, DNA fragmentation forming a "ladder" pattern upon electrophoresis (Kerr et al., British Journal of Cancer, 26: 239-257,1972). [0004] In particular, the ability to undergo apoptosis is closely associated with cancer development in that a reduction in such apoptotic ability would result in the retention of cells with unrepaired DNA damage and a consequent increased risk of mutations, which may lead to development of cancer. [0005] The p53 gene is the most frequent target of genetic alteration in human cancers. p53 plays a critical role in maintaining cellular homeostasis and tumor-free survival of the organism by modulating cell cycle progression or apoptosis (Vogelstein et al., Nature 408:307-310, 2000; Vousden et al., Nat. Rev. Cancer 2:594-604, 2002). The p53 protein functions as a transcription factor with a high affinity for specific DNA target sequences in response to DNA damage or hypoxia. It selectively destroy stressed or abnormal cells to prevent the progression to cancer (Oda et al., Cell 102:849-862, 2000). [0006] Therefore, inactivation of p53 is closely related with development of cancerous states, and such inactivation may or may not involve mutation(s) in the p53 gene. In the former case, p53 protein itself becomes non-functional due to a mutation in the p53 gene, while in the latter case, wild-type p53 protein is expressed, but the function thereof is inactivated by some other mechanism. For example, various p53 mutations including a point mutation are found in about 50% of cancer in human beings, but in many other cancer cells, p53 protein can be inactivated through an interaction with viral and cellular proteins. Therefore, in cells where the wild-type 53 protein is expressed but no longer functional, the reactivation of p53 to induce an apoptosis can provide an effective means to treat cancers. [0007] The function of p53 protein is regulated by several mechanisms, including post transcriptional modification, stabilization, protein interactions, and subcellular localization. Among them, the regulation of p53 protein stability is one of the most effective mechanisms, and in fact several oncoproteins are shown to be involved in the generation of cancer by destabilizing the p53 protein. [0008] The stability of p53, in normal cells as well as in malignant cells, is regulated by ubiquitin-dependent proteolysis, and Murine double minute 2(Mdm2) oncoprotein is the most important regulator in this process and is involved in the nuclear export and degradation of p53. Thus uncontrolled regulation of Mdm2 may give rise to a cancer cell (Ashcroft et al., Oncogene 18:7637-7643, 1999: Yang et al., Oncogene 23: 2096-2106, 2004; Boyd et al., Nat. Cell Biol.2: 563-568, 2000). The high risk human papillomavirus (HPV), which is implicated in the pathogenesis of cervical cancer, also produces E6 protein that is involved in the degradation of p53 in HPV-positive cervical cancer cells (Hausen et al., J. Natl. Cancer Inst. 92: 690-698, 2000, Hengstermann et al., Proc. Natl. Acad. Sci. U.S.A., 98: 1218-1223, 2001). A complete switch from Mdm2 to E6-dependent degradation of p53 has been shown to occur in HPV-positive cervical cancer cells. Consistent with this, the expression of peptides that specifically bind to E6 results in p53 accumulation and apoptosis in HPV-positive cancer cells (Butz et al., Proc. Natl. Acad. Sci. U.S.A., 97: 6693-6697, 2000). Therefore, for the treatment of cancer with wild-type p53 with impaired function, the reactivation of p53 to restore its apoptotic function may provide the most effective therapy. [0009] Previously, there have been many efforts to discover proteins that interact with p53 and thereby regulate its activity. For example, U.S. patent application publication No.2004/0038243 discloses p53AIP1, a regulator of apoptosis by inhibiting p53, which was discovered through a screening of genes that are induced by p53. [0010] International Patent Publication No. WO 2004/035580 discloses a low molecular weight chemical compound that was shown to be involved in recovering the apoptosis-inducing activity of p53. [0011] U.S. patent application publication No. 2004/253595 discloses p53-dependent Damage-Inducible Nuclear Protein 1 (p53DINP1) which regulates p53 by phosphorylating serine residue at position 63, thereby inducing p53-dependent apoptosis. [0012] There remains, however, a significant need for a p53 regulator with improved efficacy in modulating p53 dependent apoptosis and having the ability to interact with inactivated p53 protein and to restore its apoptotic function, which none of the above publications disclose. [0013] The information disclosed in this background of the Invention section is only for enhancement of understanding the background of the invention and therefore, unless explicitly described to the contrary, it should not be taken as an acknowledgement or any form of suggestion that this information forms the prior art that is already known in this country to a person of ordinary skill in the art. SUMMARY OF THE INVENTION [0014] The present invention has been made in an effort to provide therapy that is capable of effectively modulating apoptosis in tissues such as in tumors where the induction of apoptosis is desirable. The present inventors have discovered that Msx1 can effectively induce apoptosis in cells or tissues where the apoptosis is prevented from occurring due to an inactivation of p53 protein or absence of p53 protein. [0015] The present invention therefore contemplates the induction of apoptosis in tissues by administering to a tissue or a subject associated with a disease condition a therapeutically effective amount of an Msx1 protein or a nucleotide sequence encoding the same. [0016] The present invention further contemplates a method of modulating p53 protein activity in a tissue or a subject comprising a step of administering to a tissue or a subject associated with a disease condition a therapeutically effective amount of Msx1 protein or a nucleotide sequence encoding the same. [0017] In one aspect, said Msx1 or a nucleotide sequence encoding the same is a homeodomain region of Msx1 or a nucleotide sequence encoding the same. [0018] In another aspect, said modulation of apoptosis or p53 activity involves a direct interaction of Msx1 or homeodomain thereof with p53 protein. [0019] In a further aspect, said interaction of Msx1 or homeodomain thereof with p53 protein leads to increased stability, and/or nuclear localization of p53, which is a clear implication for modulation of apoptosis by Msx1 via control of p53. [0020] In a still further aspect, said p53 protein may be of endogenous or exogenous origin depending on the cell or tissues to be treated which may contain inactivated p53 protein or may not contain p53 at all. Continue reading... Full patent description for Novel agent for inducing apoptosis comprising msx1 or a gene encoding the same as an active ingredient Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Novel agent for inducing apoptosis comprising msx1 or a gene encoding the same as an active ingredient patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. 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