Abstract: The present invention provides NB-ARC and CARD-containing proteins (NACs), nucleic acid molecules encoding NACs and antibodies specific for at least one NAC. The invention further provides chimeric NAC proteins. The invention also provides screening assays for identifying an agent that can effectively alter the association of a NAC with a NAC-associated protein. The invention further provides methods of modulating apoptosis in a cell by introducing into the cell a nucleic acid molecule encoding a NAC or an antisense nucleotide sequence. The invention also provides a method of using a reagent that can specifically bind to a NAC to diagnose a pathology that is characterized by an increased or decreased level of apoptosis in a cell.

Abstract: Compounds that modulate the function of anti-apoptotic proteins such as Bcl-2 and Bcl-XL are identified. These compounds have the ability to convert the activity of Bcl-2-family member proteins from anti-apoptotic to pro-apoptotic. Methods for inducing apoptosis are described, together with methods for identifying molecules that induce apoptosis through interaction with Bcl-2-family members.

Abstract: In accordance with the present invention, there are provided novel Siah-Mediated-Degradation-Proteins (SMDPs) and/or SCF-Complex Proteins (SCPs). Nucleic acid sequences encoding such proteins and assays employing same are also disclosed. The invention SMDPs and/or SCPs can be employed in a variety of ways, for example, for the production of anti-SMDP and/or SCP antibodies thereto, in therapeutic compositions, and methods employing such proteins and/or antibodies for drug screening, functional genomics and other applications. Also provided are transgenic non-human mammals that express the invention protein.

Abstract: The invention provides isolated nucleic acid molecules encoding PAAD-domain containing polypeptides and functional fragments thereof, including fragments containing PAAD domains, NB-ARC domains and LRR domains, encoded polypeptides, and antibodies. Also provided are methods of identifying polypeptides and agents that associate with a PAAD-domain containing polypeptide or fragment thereof, or that alter an association of a PAAD domain-containing polypeptides. Further provided are methods of identifying agents that modulate PAAD domain-mediated inhibition of NFkB activity, or modulate an activity of an NB-ARC domain of a PAAD domain-containing polypeptide. Also provided are methods of modulating NFkB transcriptional activity in a cell, and methods of altering expression of a PAAD domain-containing polypeptide in a cell.

Abstract: Novel methods of regulating cellular apoptosis by affecting the interaction of hepatitis B X-interacting protein (HBXIP) with Survivin are described. More specifically, these novel methods of enhancing apoptosis of neoplastic cells comprises inhibiting interaction of hepatitis B X-interacting protein (HBXIP) with Survivin.

Abstract: The present invention provides a family of BAG-1 related proteins from humans (BAG-1L, BAG-1, BAG-2, BAG-3, BAG-4 and BAG-5), the invertebrate C. elegans (BAG-1, BAG-2) and the fission yeast S. pombe (BAG-1A, BAG-1B) and the nucleic acid molecules that encode them.

Abstract: The present invention provides a family of BAG-1 related proteins from humans (BAG-1L, BAG-1, BAG-2, BAG-3, BAG-4 and BAG-5), the invertebrate C. elegans (BAG-1, BAG-2) and the fission yeast S. pombe (BAG-1A, BAG-1B) and the nucleic acid molecules that encode them.

Abstract: The invention provides isolated Bcl-2 domain-containing polypeptides from Mycobacterial species, including M. tuberculosis, M. avium, M. bovis, M. leprae and M. smegmatis, and from Streptomyces species, including S. coelicolor, as well as modifications of such polypeptides, functional fragments therefrom, encoding nucleic acid molecules and specific antibodies. Also provided are methods for identifying polypeptides and compounds that associate with or modulate the activity of the Bcl-2 domain-containing polypeptides. Further provided are methods of modulating apoptosis and treating pathological conditions using the described nucleic acid molecules, polypeptides and compounds.

Abstract: The invention provides isolated nucleic acid molecules encoding PAAD-domain containing polypeptides and functional fragments thereof, including fragments containing PAAD domains, NACHT domains and ARED domains, encoded polypeptides, and antibodies. Also provided are methods of identifying polypeptides and agents that associate with a PAAD-domain containing polypeptide or fragment thereof, or that alter an association of a PAAD domain-containing polypeptides. Further provided are methods of identifying agents that modulate PAAD domain-mediated inhibition of NF&kgr;B activity, or modulate an activity of a NACHT domain of a PAAD domain-containing polypeptide.

Abstract: The invention provide a method of identifying a biomarker that is diagnostic for survival of a patient with a prostate neoplastic condition. The method consists of (a) measuring the level of IAPs in a neoplastic prostate cell-containing sample from patients with a prostate neoplastic condition, and (b) identifying a correlation between the level of IAPs in a sample from a patient with the survival of that patient, where the correlation of an IAP with survival in patients indicates the IAP is a biomarker diagnostic of survival of a patient with a prostate neoplastic condition. Also provided is a method of determining a prognosis for survival for a patient with a prostate neoplastic condition. The method consists of (a) measuring the level of XIAP in a neoplastic prostate cell-containing sample from the patient, and (b) comparing the level of XIAP in the sample to a reference level of XIAP, where an increased level of XIAP in the sample correlates with increased survival of the patient.

Abstract: The invention provides isolated SUMO-specific protease-like (or “SSP”) domain-containing polypeptides from microorganisms, including bacteria, protozoans and yeast, including Eschericia, Salmonella, Pseudomonas, Chlamydia, Plasmodium, Trypanosma, Mesorhizobium, Rickettsia, Cryptosporidium and Candida species, as well as modifications of such polypeptides, functional fragments therefrom, encoding nucleic acid molecules and specific antibodies. Also provided are methods for identifying polypeptides and compounds that associate with or modulate the activity of the SSP domain-containing polypeptides. Further provided are methods of modulating a biological activity in a cell, and treating pathological conditions, using the described nucleic acid molecules, polypeptides and compounds.

Abstract: In accordance with the present invention, there are provided novel Siah-Mediated-Degradation-Proteins (SMDPs) and/or SCF-Complex Proteins (SCPs). Nucleic acid sequences encoding such proteins and assays employing same are also disclosed. The invention SMDPs and/or SCPs can be employed in a variety of ways, for example, for the production of anti-SMDP and/or SCP antibodies thereto, in therapeutic compositions, and methods employing such proteins and/or antibodies for drug screening, functional genomics and other applications. Also provided are transgenic non-human mammals that express the invention protein.

Abstract: The present invention provides a family of BAG-1 related proteins from humans (BAG-1L, BAG-1, BAG-2, BAG-3, BAG-4 and BAG-5), the invertebrate C. elegans (BAG-1, BAG-2) and the fission yeast S. pombe (BAG-1A, BAG-1B) and the nucleic acid molecules that encode them.

Abstract: The invention provides isolated agents having a core peptide selected from the group consisting of Core peptides 5 through 39 and 42 through 55, wherein the agent derepresses an IAP-inhibited caspase. Also provided is an isolated agent having a core structure selected from any of the structures shown in FIGS. 5, 9, 10, 14B, and 21-24 wherein said agent derepresses an IAP-inhibited caspase. The invention further provides a method of derepressing an IAP-inhibited caspase. The method consists of contacting an IAP-inhibited caspase with an effective amount of an agent to derepress an IAP-inhibited caspase, the agent having a core motif selected from the group consisting of a core peptide having a sequence set forth in any of Core peptides 4 through 39 and 42 through 55, and a core structure selected from the group consisting of TPI759, TPI882, TPI914 or TPI927.

Abstract: The invention provides a method of identifying an effective compound that modulates the binding of Humanin to Bax or Bid. The invention also provides a method of identifying an effective compound that modulates an activity of Bax or Bid. In addition, the invention provides a method of identifying a Humanin-like compound that binds to Bax or Bid or modulates an activity of Bax or Bid, or inhibits the apoptotic activity of Bax or Bid. The invention further provides an isolated polypeptide containing a mitochondrial-derived form of Humanin (SEQ ID NO:3) or a functional fragment thereof where the fragment contains the methionine at position 16 of SEQ ID NO:3.

Abstract: ABSTRACT A novel human member of the Bcl-2 family Bcl-B has been identified, which is closest in amino-acid sequence homology to the Boo (Diva) protein. The Bcl-B protein is widely expressed in adult human tissues. The Bcl-B protein modulates apoptosis. Bcl-B also binds Bcl-2, BCI-XL, and Bax but not Bak. Bcl-B displays a unique pattern of selectivity for binding and regulating the function of other members of the Bcl-2 family.

Abstract: The invention provides a method for promoting cell differentiation, which involves modifying a cell to increase expression of a BAG polypeptide that promotes differentiation of a cell, such as a neuronal cell, stem cell or neural progenitor cell. The invention provides another method for promoting cell differentiation, which involves modifying a cell to increase the amount of a nuclear localized BAG polypeptide, when the nuclear localized BAG polypeptide promotes differentiation of the cell. The invention also provides methods for reducing the rate of cell proliferation and suppressing apoptosis. The methods involve modifying a cell to increase the amount of a nuclear localized BAG polypeptide, when the nuclear localized BAG polypeptide inhibits proliferation, or suppresses apoptosis, respectively.

Abstract: The invention provides methods for determining a prognosis for survival for a cancer patient. One method involves (a) measuring a level of a TUCAN in a neoplastic cell-containing sample from the cancer patient, and (b) comparing the level of TUCAN in the sample to a reference level of TUCAN, wherein a low level of TUCAN in the sample correlates with increased survival of the patient. Another method involves (a) measuring a level of TUCAN in a neoplastic cell-containing sample from the cancer patient, and (b) classifying the patient as belonging to either a first or second group of patients, wherein the first group of patients having low levels of TUCAN is classified as having an increased likelihood of survival compared to the second group of patients having high levels of TUCAN.

Abstract: The invention provides isolated nucleic acid molecules encoding PAAD-domain containing polypeptides and functional fragments thereof, including fragments containing PAAD domains, NB-ARC domains and LRR domains, encoded polypeptides, and antibodies. Also provided are methods of identifying polypeptides and agents that associate with a PAAD-domain containing polypeptide or fragment thereof, or that alter an association of a PAAD domain-containing polypeptides. Further provided are methods of identifying agents that modulate PAAD domain-mediated inhibition of NF&kgr;B activity, or modulate an activity of an NB-ARC domain of a PAAD domain-containing polypeptide. Also provided are methods of modulating NF&kgr;B transcriptional activity in a cell, and methods of altering expression of a PAAD domain-containing polypeptide in a cell.

Abstract: The invention provides a method of treating a disease or pathological condition resulting in apoptotic cell death. The method includes increasing the activity of Bcl-2 in cells affected by the disease or pathological condition. Diseases or pathological conditions can include, for example, neurodegenerative diseases, cancer and viral infections. Also provided is a method of prolonging the in vivo survival of transplanted cells for the treatment of a disease or pathological condition. The method includes increasing the activity of Bcl-2 in a population of cells and transplanting the population of cells having increased Bcl-2 activity into a subject. Diseases or pathological conditions can include, for example, neurodegenerative diseases, cancer and viral infections. A method to enhance the sensitivity of malignant cells to therapy is provided that includes decreasing the activity of Bcl-2 in the malignant cells.