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MCL1
Induced myeloid leukemia cell differentiation protein Mcl-1 is a protein that in humans is encoded by the ''MCL1'' gene. Function The protein encoded by this gene belongs to the Bcl-2 family. Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified. The longer gene product (isoform 1) enhances cell survival by inhibiting apoptosis while the alternatively spliced shorter gene product (isoform 2) promotes apoptosis and is death-inducing. The protein MCL1 has a very short biological half-life of only 20–30 minutes. The loss of MCL1 has a more dramatic impact than the loss of any other anti-apoptotic member of the Bcl-2 family. Loss of the ''Mcl-1'' gene results in embryo death when the embryo is only around 3.5 days old, before it has even implanted. Conditional deletion of ''Mcl-1'' depletes a wide variety of cells, including hematopoietic stem cells, B cell–committed progenitors, T cell–committed progenitors, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
TCTP
Translationally Controlled Tumor Protein (TCTP) is a protein that in humans is encoded by the ''TPT1'' gene. The ''TPT1'' gene is mapped 13q12-q1413 in the Chromosome 13. The human gene contains five introns and six exons, The TPT1-gene contains a promoter with a canonical TATA-box and several promoter elements, which are well-conserved in mammals. The assay with reporter gene exhibits a strong promoter activity comparable to viral promoters. TCTP protein is also referred to as Q23, P21, P23, histamine releasing factor (HRF), and fortilin. TCTP is a multifunctional and highly conserved protein that existed ubiquitously in different eukaryote species and distributed widely in various tissues and cell types. Human translationally controlled tumor protein (hTCTP) is a growth-related, calcium-binding protein. History Translationally controlled tumor protein was first discovered in 1989 as a cDNA sequence obtained from a human mammary carcinoma cDNA library with proves deri ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PCNA
Proliferating cell nuclear antigen (PCNA) is a DNA clamp that acts as a processivity factor for DNA polymerase δ in eukaryotic cells and is essential for replication. PCNA is a homotrimer and achieves its processivity by encircling the DNA, where it acts as a scaffold to recruit proteins involved in DNA replication, DNA repair, chromatin remodeling and epigenetics. Many proteins interact with PCNA via the two known PCNA-interacting motifs PCNA-interacting peptide (PIP) box and AlkB homologue 2 PCNA interacting motif (APIM). Proteins binding to PCNA via the PIP-box are mainly involved in DNA replication whereas proteins binding to PCNA via APIM are mainly important in the context of genotoxic stress. Function The protein encoded by this gene is found in the nucleus and is a cofactor of DNA polymerase delta. The encoded protein acts as a homotrimer and helps increase the processivity of leading strand synthesis during DNA replication. In response to DNA damage, this protein is ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BCL2L11
Bcl-2-like protein 11, commonly called BIM (Bcl-2 Interacting Mediator of cell death), is a protein that in humans is encoded by the ''BCL2L11'' gene. Function The protein encoded by this gene belongs to the BCL-2 protein family. BCL-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. The protein encoded by this gene contains a Bcl-2 homology domain 3 (BH3). It has been shown to interact with other members of the BCL-2 protein family, including BCL2, BCL2L1/BCL-X(L), and MCL1, and to act as an apoptotic activator. The expression of this gene can be induced by nerve growth factor (NGF), as well as by the forkhead transcription factor FKHR-L1 (FoxO3a), which suggests a role of this gene in neuronal and lymphocyte apoptosis. Transgenic studies of the mouse counterpart suggested that this gene functions as an essential initiator of apoptosis in thymocyte-negative selection. Several alte ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Bcl-2
Bcl-2 (B-cell lymphoma 2), encoded in humans by the ''BCL2'' gene, is the founding member of the Bcl-2 family of regulator proteins that regulate cell death (apoptosis), by either inhibiting (anti-apoptotic) or inducing (pro-apoptotic) apoptosis. It was the first apoptosis regulator identified in any organism. Bcl-2 derives its name from ''B-cell lymphoma 2'', as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in follicular lymphomas. Orthologs (such as ''Bcl2'' in mice) have been identified in numerous mammals for which complete genome data are available. Like BCL3, BCL5, BCL6, BCL7A, BCL9, and BCL10, it has clinical significance in lymphoma. Isoforms The two isoforms of Bcl-2, Isoform 1, and Isoform 2, exhibit a similar fold. However, results in the ability of these isoforms to bind to the BAD and BAK proteins, as well as in the structural topology and electrostatic potential of the binding ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BAK1
Bcl-2 homologous antagonist/killer is a protein that in humans is encoded by the ''BAK1'' gene on chromosome 6. The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form oligomers or heterodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein localizes to mitochondria, and functions to induce apoptosis. It interacts with and accelerates the opening of the mitochondrial voltage-dependent anion channel, which leads to a loss in membrane potential and the release of cytochrome c. This protein also interacts with the tumor suppressor P53 after exposure to cell stress. Structure BAK1 is a pro-apoptotic Bcl-2 protein containing four Bcl-2 homology (BH) domains: BH1, BH2, BH3, and BH4. These domains are composed of nine α-helices, with a hydrophobic α-helix core surrounded by amphipathic helices and a transmembrane C-terminal α-helix anchored to the mitochondrial outer membran ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Bcl-2 Family
The Bcl-2 familyTC# 1.A.21 consists of a number of evolutionarily-conserved proteins that share Bcl-2 homology (BH) domains. The Bcl-2 family is most notable for their regulation of apoptosis, a form of programmed cell death, at the mitochondrion. The Bcl-2 family proteins consists of members that either promote or inhibit apoptosis, and control apoptosis by governing mitochondrial outer membrane permeabilization (MOMP), which is a key step in the intrinsic pathway of apoptosis. A total of 25 genes in the Bcl-2 family were identified by 2008. Structure Bcl-2 family proteins have a general structure that consists of a hydrophobic α-helix surrounded by amphipathic α-helices. Some members of the family have transmembrane domains at their c-terminus which primarily function to localize them to the mitochondrion. Bcl-x(L) is 233 amino acyl residues (aas) long and exhibits a single very hydrophobic putative transmembrane α-helical segment (residues 210-226) when in the membrane. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
TNKS
Tankyrase, also known as tankyrase 1, is an enzyme that in humans is encoded by the ''TNKS'' gene. It inhibits the binding of TERF1 to telomeric DNA. Tankyrase attracts substantial interest in cancer research through its interaction with AXIN1 and AXIN2, which are negative regulators of pro-oncogenic β-catenin signaling. Importantly, activity in the β-catenin destruction complex can be increased by tankyrase inhibitors and thus such inhibitors are a potential therapeutic option to reduce the growth of β-catenin-dependent cancers. Description Tankyrase-1 is a poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking. Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation (PARylation) of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degrada ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phorbol-12-myristate-13-acetate-induced Protein 1
Phorbol-12-myristate-13-acetate-induced protein 1 is a protein that in humans is encoded by the ''PMAIP1'' gene, and is also known as Noxa. Noxa (Latin for ''damage'') is a pro-apoptotic member of the Bcl-2 protein family. Bcl-2 family members can form hetero- or homodimers, and they act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. The expression of Noxa is regulated by the tumor suppressor p53, and Noxa has been shown to be involved in p53-mediated apoptosis. Interactions Noxa has been shown to interact with: * BCL2-like 1, * Bcl-2, and * MCL1. See also * Apoptosis * Apoptosome * Bcl-2 * Bcl-2-associated X protein (BAX) * BH3 interacting domain death agonist (BID) * Caspases * Cytochrome c * Mitochondrion * p53 upregulated modulator of apoptosis The p53 upregulated modulator of apoptosis (PUMA) also known as Bcl-2-binding component 3 (BBC3), is a pro-apoptotic protein, member of the Bcl-2 protein family. In huma ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
DAD1
Dolichyl-diphosphooligosaccharide—protein glycosyltransferase subunit DAD1 is an enzyme that in humans is encoded by the ''DAD1'' gene. Function DAD1, the defender against apoptotic cell death, was initially identified as a negative regulator of programmed cell death in the temperature sensitive tsBN7 cell line. The DAD1 protein disappeared in temperature-sensitive cells following a shift to the nonpermissive temperature, suggesting that loss of the DAD1 protein triggered apoptosis. DAD1 is believed to be a tightly associated subunit of oligosaccharyltransferase both in the intact membrane and in the purified enzyme, thus reflecting the essential nature of N-linked glycosylation in eukaryotes. Interactions DAD1 has been shown to interact with MCL1 Induced myeloid leukemia cell differentiation protein Mcl-1 is a protein that in humans is encoded by the ''MCL1'' gene. Function The protein encoded by this gene belongs to the Bcl-2 family. Alternative splicing occurs a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Bcl-2-associated Death Promoter
The BCL2 associated agonist of cell death (BAD) protein is a pro-apoptotic member of the Bcl-2 gene family which is involved in initiating apoptosis. BAD is a member of the BH3-only family, a subfamily of the Bcl-2 family. It does not contain a C-terminal transmembrane domain for outer mitochondrial membrane and nuclear envelope targeting, unlike most other members of the Bcl-2 family. After activation, it is able to form a heterodimer with anti-apoptotic proteins and prevent them from stopping apoptosis. Mechanism of action Bax/ Bak are believed to initiate apoptosis by forming a pore in the mitochondrial outer membrane that allows cytochrome c to escape into the cytoplasm and activate the pro-apoptotic caspase cascade. The anti-apoptotic Bcl-2 and Bcl-xL proteins inhibit cytochrome c release through the mitochondrial pore and also inhibit activation of the cytoplasmic caspase cascade by cytochrome c. Dephosphorylated BAD forms a heterodimer with Bcl-2 and Bcl-xL, inactivati ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BH3 Interacting Domain Death Agonist
The BH3 interacting-domain death agonist, or BID, gene is a pro-apoptotic member of the Bcl-2 protein family. Bcl-2 family members share one or more of the four characteristic domains of homology entitled the Bcl-2 homology (BH) domains (named BH1, BH2, BH3 and BH4), and can form hetero- or homodimers. Bcl-2 proteins act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. Interactions BID is a pro-apoptotic Bcl-2 protein containing only the BH3 domain. In response to apoptotic signaling, BID interacts with another Bcl-2 family protein, Bax, leading to the insertion of Bax into organelle membranes, primarily the outer mitochondrial membrane. Bax is believed to interact with, and induce the opening of the mitochondrial voltage-dependent anion channel, VDAC. Alternatively, growing evidence suggest that activated Bax and/or Bak form an oligomeric pore, MAC in the outer membrane. This results in the release of cytochrome c and other pr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Seliciclib
Seliciclib (roscovitine or CYC202) is an experimental drug candidate in the family of pharmacological cyclin-dependent kinase (CDK) inhibitors that preferentially inhibit multiple enzyme targets including CDK2, CDK7 and CDK9, which alter the growth phase or state within the cell cycle of treated cells. Seliciclib is being developed by Cyclacel.This is a phase II, dose ranging, multicenter, randomized, double-blind, placebo-controlled study. The aim of this study is to assess the safety of increasing doses of roscovitine administered orally for 4 cycles of 4 consecutive days (treatment "on") separated by a 3 days treatment free period (treatment "off") in adult CF subjects with Cystic Fibrosis carrying 2 Cystic Fibrosis causing mutations with at least one F508del-CFTR mutation and chronically infected with Pseudomonas aeruginosa. This study involved 36 Cystic Fibrosis patients: 24 treated and 12 controls. Seliciclib is being researched for the treatment of non-small cell lung can ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
