Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
2001-09-10
2002-10-29
Myers, Carla J. (Department: 1634)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C536S023100, C536S024310, C536S024100, C536S024200
Reexamination Certificate
active
06472517
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a purified or isolated polynucleotide encoding human CIDE B protein, the regulatory nucleic acids contained therein, polymorphic markers thereof, and the resulting encoded protein, as well as to methods and kits for detecting this polynucleotide and this protein. The present invention also pertains to a polynucleotide carrying the natural regulatory regions of the CIDE B gene which is useful, for example, to express a heterologous nucleic acid in host cells or host organisms as well as functionally active regulatory polynucleotides derived from said regulatory regions.
BACKGROUND OF THE INVENTION
Apoptosis is of fundamental importance to biological processes including embryogenesis, maintenance of tissue homeostasis, normal cellular development of multicellular organisms, elimination of virus-infected cells, and the development of immune system. It is a type of death that is fundamentally distinct from degenerative death or necrosis in that it is an active process of gene-directed cellular self-destruction which, in some instances serves a biologically meaningful homeostatic function. Necrosis, in contrast, is cell death occurring as a result of severe injurious changes in the environment of infected cells.
Morphologically, apoptosis is characterized by the rapid condensation of the cell with preservation of membranes. Synchronistically with the compaction of chromatin, several biochemical changes occur in the cell. Nuclear DNA is cleaved at the linker regions between nucleosomes to produce fragments that are easily demonstrated by agarose gel electrophoresis wherein a characteristic ladder develops.
The primary image of apoptosis is that of the dying thymocyte: fusion of chromatin into one mass, which binds to the nuclear membrane, while the cytoplasm remains apparently intact before beginning to condense. The nuclear change is one of the earliest visible processes; the conversion to the condensed state occurs rapidly and is accompanied by endonucleolytic degradation of DNA between nucleosomes. Once the chromatin has condensed, electrophoresis of the DNA demonstrates a ladder of fragments differing in size by 180 bp, generated by an enzymatic activity resembling that of DNase I.
This type of cell death is seen in many varieties of cells, especially those that, like lymphocytes or thymocytes, have relatively little cytoplasm and are highly mitotic or derive from highly mitotic lines. In this situation, in which mitotic cells are likely to face challenges by mutagens (viruses, toxins), an appropriate biological imperative would be to destroy the DNA rapidly and effectively. Thus, this type of cell death is particularly dramatic among hematopoietic cells and their derivatives.
Several regulatory components of the apoptotic pathway have been identified in various living organisms including man and the nematode
Caenorhabditis elegans.
Two murine transcription products involved in cell apoptosis have been reported by Inohara et al. (1998), that have been named respectively CIDE-A and CIDE-B. Murine CIDE-A and CIDE-B have strong homology with the murine anti-apoptosis DFF45 protein as well as with the drosophila protein DREP-1. The homology of CIDE-A, CIDE-B and FSP27 with DFF45 was restricted to an N-terminal region designated by Inohara et al. as CIDE-N domain which showed 39, 29 and 38% amino acid identity respectively with DFF45.
Because there is a strong need in the art to make available to the public novel means useful to prevent or inhibit apoptosis disorders, either in the case of disorders caused by abnormal cell proliferation wherein apoptosis induction is desirable or in the case of disorders caused by abnormal cell death wherein an inhibition or an arrest of apoptosis is desirable, the inventors have attempted to isolate and characterize a novel gene encoding a protein involved in apoptosis pathway, namely the human CIDE-B gene.
SUMMARY OF THE INVENTION
The present invention pertains to a nucleic acid molecule comprising the genomic sequence of the human CIDE B gene. The CIDE B genomic sequence comprises regulatory sequences located both upstream (5′-end) and downstream (3′-end) of the transcribed portion of said gene, these regulatory sequences being also part of the invention.
The invention also deals with the complete cDNA sequence encoding the CIDE B protein, as well as with the corresponding translation product.
Oligonucleotide probes or primers hybridizing specifically with a CIDE B genomic or cDNA sequence are also part of the present invention.
A further object of the invention consists of recombinant vectors comprising any of the nucleic acid sequences above described, and in particular of recombinant vectors comprising a CIDE B regulatory sequence or a sequence encoding a CIDE B protein, as well as of cell hosts comprising said nucleic acid sequences or recombinant vectors.
Finally, the invention is directed to methods for the screening of substances or molecules which modulate the expression of CIDE B.
The invention is also directed to biallelic markers that are located within the CIDE B genomic sequence, these biallelic markers representing useful tools in order to identify a statistically significant association between specific alleles of CIDE B gene and one or several disorders related to apoptosis such as cancer and AIDS.
REFERENCES:
patent: WO 93/16178 (1993-08-01), None
patent: WO 99/55134 (1999-11-01), None
Strausberg, R. National Center for Biotechnical Information, National Library of Medicine, NIH (Bethesda, MD, USA) 1998, Accession No. A1051238.*
Strausberg, R. National Center for Biotechnical Information, National Library of Medicine, NIH (Bethesda, MD, USA) 1997, Accession No. AA283696.*
Inohara, et al.; “CIDE, a novel family of cell death activators with homology to the 45 kDa subunit of the DNA fragmentation factor”; The EMBO Journal, vol. 17, No. 9, pp. 2526-2533, 1998; XP-002133431; Oxford University Press.
Inohara, et al.; “CIDE, a novel family of cell death activators with homology to the 45 kDa subunit fo the DNA fragmentation factor”; The EMBO Journal, vol. 17, No. 9, pp. 2526-2533, 1998; XP-000882759; Oxford University Press.
Database EMBL 'Online!; accession No. A1051238; Strausberg; “NCI/CGAP, tumor gene index: . . . similar to . . . cell death-inducing DNA fragmentation factor, alpha subunit-like effector B”; XP-002133432; abstract.
Database EMBL 'Online!; accession No. AW024578; Sep. 14, 1999; Strausberg; “NCI/CGAP, tumor gene index: . . . similar to . . . cell death-inducing DNA fragmentation factor, alpha subunit-like effector B.”; XP-002133433; abstract.
Xiong, Etal.; “Biallelic markers in genetics studies of human diseases: their power, accuracy, and density in population-based linikage analyses”; American Journal of Human Genetics (Oct. 1997), vol. 61, No. 4, Suppl., pp. A301; 47th Annual Meeting of the American Society of Human Genetics, Baltimore, MD, XP-000852591.
Kruglyak, Leonid; “The use of a genetic map of biallelic markers in linkage studies”; Nature Genetics, vol. 17, Sep. 1977, p. 21-4; XP-000882279.
Database EMBL 'Online!; accession No. p56198/ID FS27_mouse; Nov. 1, 1997; Danesch, et al.; “Fat-specific protein FSP27”; XP-002133434.
Genset S.A.
Johns Carol
Lucas John
Myers Carla J.
LandOfFree
Nucleic acids encoding human CIDE-B protein and polymorphic... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Nucleic acids encoding human CIDE-B protein and polymorphic..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Nucleic acids encoding human CIDE-B protein and polymorphic... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2939584