Bcl-2-like protein 15, also known as Bfk, is a member of the bcl2 gene family. It is highly expressed in the epididymis in mouse []and in tissues of the gastrointestinal tract, where it may help to protect against the development of gastrointestinal malignancy [].
Bax inhibitor-1 (BI-1) (gene TEGT) []is a suppressor of apoptosis that interacts with BCL2 and BCL-X. These are proteins of about 25kDa which seem to contain seven transmembrane domains. Homologues are found in plants and bacteria.This entry corresponds to a conserved region that starts with the beginning of the third transmembrane domain and endsin the middle of the fourth one.
Prostate apoptosis response 4 (Par-4) induced apoptosis of selective prostate cancer cells PC-3, DU-145, and TSU-Pr and caused tumor regression by inhibition of NF-kappaB activity and cell membrane trafficking of Fas and FasL that leads to the activation of the Fas-Fas-associated death domain-caspase-8 pro-death pathway []. It modulates transcription and growth suppression functions of the Wilms' tumor suppressor WT1. It down-regulates the anti-apoptotic protein BCL2 via its interaction with WT1 []. Par-4 also regulates the amyloid precursor protein (APP) cleavage activity of BACE1 [].
Bax inhibitor-1 (BI-1) []is a suppressor of apoptosis that interacts with BCL2 and BCL-X. Human Bax BI-1 is an evolutionarily conserved integral membrane protein containing multiple membrane-spanning segments localised to the ER membrane. It has 6-7 membrane-spanning domains. The C termini of the mammalian BI-1 proteins are comprised of basic amino acids resembling some nuclear targeting sequences, but otherwise the predicted proteins lack motifs that suggest this function. BI-1 also regulates cell death triggered by ER stress [, , ]. BI-1 appears to exert its effect through an interaction with calmodulin []. Crystal structure of a bacterial member reveals that these proteins mediate a calcium leak across the membrane in a pH-dependent manner. Calcium homoeostasis balances passive calcium leak with active calcium uptake. The structure exists in a pore-closed and pore-open conformation, at pHs of 8 and 6 respectively [, ].This entry represents BI-1 and related sequences, including lifeguard proteins, which resemble BI-1 and also act as apoptotic regulators [].
Tumor necrosis factor receptor superfamily member 4 (TNFRSF4), also known as OX40, ACT35, CD134, IMD16 or TXGP1L, activates NF-kappaB through its interaction with adaptor proteins TRAF2 and TRAF5 []. It also promotes the expression of apoptosis inhibitors BCL2 and BCL2lL1/BCL2-XL, and thus suppresses apoptosis []. It is primarily expressed on activated CD4+ and CD8+ T cells, where it is transiently expressed and upregulated on the most recently antigen-activated T cells within inflammatory lesions. This makes it an attractive target to modulate immune responses, i.e. TNFRSF4 (OX40) blocking agents to inhibit adverse inflammation or agonists to enhance immune responses [, ]. An artificially created biologic fusion protein, OX40-immunoglobulin (OX40-Ig), prevents OX40 from reaching the T-cell receptors, thus reducing the T-cell response. Some single nucleotide polymorphisms (SNPs) of its natural ligand OX40 ligand (OX40L, CD252), which is also found on activated T cells, have been associated with systemic lupus erythematosus [].This entry represents the N-terminal domain of TNFRSF4. TNF-receptors are modular proteins. The N-terminal extracellular part contains a cysteine-rich region responsible for ligand-binding. This region is composed of small modules of about 40 residues containing 6 conserved cysteines; the number of modules can vary in number and type in different members of the family [, , ].
B cell CLL/lymphoma-2 (Bcl-2) and related proteins comprise the Bcl-2 family. Bcl-2 proteins are central regulators of caspase activation, and play a key role in cell death by regulating the integrity of the mitochondrial and endoplasmic reticulum (ER) membranes []. Though originally characterised with respect to their roles in controlling outer mitochondrial membrane integrity and apoptosis, the members of the Bcl-2 family are involved in numerous cellular pathways [].Bcl-2 and its relatives are functionally classified as either antiapoptoticor proapoptotic. All members contain at least one of four conserved motifs, termed Bcl-2 Homology (BH) domains. Antiapoptotic BCL-2 proteins contain four Bcl-2 homology domains (BH1-4). The major antiapoptotic proteins are Bcl-2-related gene A1 (A1), Bcl-2, Bcl-2-related gene, long isoform (Bcl-xL), Bcl-w, and myeloid cell leukemia 1 (MCL-1). They preserve outer mitochondrial membrane (OMM) integrity by directly inhibiting the proapoptotic Bcl-2 proteins [].The proapoptotic Bcl-2 members are divided into the effector proteins and the BH3-only proteins. The effector proteins Bcl-2 antagonist killer 1 (BAK) and Bcl-2-associated x protein (BAX) were originally described to contain only BH1-3; however, structure-based alignments revealed a conserved BH4 motif []. Upon activation BAK and BAX homo-oligomerise into proteolipid pores within the OMM to promote MOMP (mitochondrial outer membrane permeabilisation). The BH3-only proteins function in distinct cellular stress scenarios and are subdivided based on their ability to interact with the antiapoptotic or both the antiapoptotic and the effector proteins [].Bcl-2-associated x protein (BAX) is a proapoptotic member of the Bcl-2 family. It accelerates programmed cell death by binding to, and antagonising the apoptosis repressor Bcl2 [, ].
B cell CLL/lymphoma-2 (Bcl-2) and related proteins comprise the Bcl-2 family. Bcl-2 proteins are central regulators of caspase activation, and play a key role in cell death by regulating the integrity of the mitochondrial and endoplasmic reticulum (ER) membranes []. Though originally characterised with respect to their roles in controlling outer mitochondrial membrane integrity and apoptosis, the members of the Bcl-2 family are involved in numerous cellular pathways [].Bcl-2 and its relatives are functionally classified as either antiapoptoticor proapoptotic. All members contain at least one of four conserved motifs, termed Bcl-2 Homology (BH) domains. Antiapoptotic BCL-2 proteins contain four Bcl-2 homology domains (BH1-4). The major antiapoptotic proteins are Bcl-2-related gene A1 (A1), Bcl-2, Bcl-2-related gene, long isoform (Bcl-xL), Bcl-w, and myeloid cell leukemia 1 (MCL-1). They preserve outer mitochondrial membrane (OMM) integrity by directly inhibiting the proapoptotic Bcl-2 proteins [].The proapoptotic Bcl-2 members are divided into the effector proteins and the BH3-only proteins. The effector proteins Bcl-2 antagonist killer 1 (BAK) and Bcl-2-associated x protein (BAX) were originally described to contain only BH1-3;however, structure-based alignments revealed a conserved BH4 motif []. Upon activation BAK and BAX homo-oligomerise into proteolipid pores within the OMM to promote MOMP (mitochondrial outer membrane permeabilisation). The BH3-only proteins function in distinct cellular stress scenarios and are subdivided based on their ability to interact with the antiapoptotic or both the antiapoptotic and the effector proteins [].Bcl-2 homologue antagonist/killer (BAK) is a proapoptotic member of the Bcl-2 family. In the presence of an appropriate stimulus, accelerates programmed cell death by binding to, and antagonizing the anti-apoptotic action of Bcl2 or its adenovirus homologue E1B 19k protein. Low micromolar levels of zinc ions inhibit the promotion of apoptosis [, ].
B cell CLL/lymphoma-2 (Bcl-2) and related proteins comprise the Bcl-2 family. Bcl-2 proteins are central regulators of caspase activation, and play a key role in cell death by regulating the integrity of the mitochondrial and endoplasmic reticulum (ER) membranes []. Though originally characterised with respect to their roles in controlling outer mitochondrial membrane integrity and apoptosis, the members of the Bcl-2 family are involved in numerous cellular pathways [].Bcl-2 and its relatives are functionally classified as either antiapoptoticor proapoptotic. All members contain at least one of four conserved motifs, termed Bcl-2 Homology (BH) domains. Antiapoptotic BCL-2 proteins contain four Bcl-2 homology domains (BH1-4). The major antiapoptotic proteins are Bcl-2-related gene A1 (A1), Bcl-2, Bcl-2-related gene, long isoform (Bcl-xL), Bcl-w, and myeloid cell leukemia 1 (MCL-1). They preserve outer mitochondrial membrane (OMM) integrity by directly inhibiting the proapoptotic Bcl-2 proteins [].The proapoptotic Bcl-2 members are divided into the effector proteins and the BH3-only proteins. The effector proteins Bcl-2 antagonist killer 1 (BAK) and Bcl-2-associated x protein (BAX) were originally described to contain only BH1-3; however, structure-based alignments revealed a conserved BH4 motif []. Upon activation BAK and BAX homo-oligomerise into proteolipid pores within the OMM to promote MOMP (mitochondrial outer membrane permeabilisation). The BH3-only proteins function in distinct cellular stress scenarios and are subdivided based on their ability to interact with the antiapoptotic or both the antiapoptotic and the effector proteins [].This entry represents the Bcl2 family and related proteins, including E1B 19K protein (also known as E1B protein, small T-antigen), which is a putative adenovirus Bcl-2 homologue that inhibits E1A induced apoptosis and hence prolongs the viability of the host cell.
