Transcription factor activator protein (AP)-1, comprising Jun (c-Jun, JunB, and JunD) and Fos (c-Fos, FosB, Fra1, and Fra2) family members, plays a central role in regulating gene transcription in various biological processes []. Fos protein family members are involved in rodent fibroblasts transformation []. Fos protein family members form stable heterodimers with Jun proteins and thereby enhance their DNA-bindingactivity [].This entry represents fos-related antigen 1 (Fra1). It is an activator of bone matrix formation []and can negatively regulate pulmonary fibrosis in vivo []. It is overexpressed in breast cancer cells and may be a possible biomarker for prognosis of breast cancer [].
Transcription factor activator protein (AP)-1, comprising Jun (c-Jun, JunB, and JunD) and Fos (c-Fos, FosB, Fra1, and Fra2) family members, plays a central role in regulating gene transcription in various biological processes []. Fos protein family members form stable heterodimerswith Jun proteins and thereby enhance their DNA-bindingactivity []. This entry reprsents FosB []. FosB-null mice display impaired adult hippocampal neurogenesis and spontaneous epilepsy with depressive behavior [].
Transcription factor activator protein (AP)-1, comprising Jun (c-Jun, JunB, and JunD) and Fos (c-Fos, FosB, Fra1, and Fra2) family members, plays a central role in regulating gene transcription in various biological processes []. Fos protein family members are involved in rodent fibroblasts transformation []. Fos protein family members form stable heterodimers with Jun proteins and thereby enhance their DNA-bindingactivity [].This entry represents the c-Fos and v-Fos proteins. c-Fos is the human homologue of the retroviral oncogene v-Fos. c-Fos can regulate growth not only by its transcription-factor activity, but also through mechanisms independent of its genomic AP-1 activity. By association with particular enzymes, it can act as a cytoplasmic activator of the biosynthesis of lipids both in normal and pathological cellular processes []. In the nucleus, where lipid synthesis also occurs, it binds to PI4P5K (phosphatidylinositol-4-monophosphate 5-kinase) and activates nuclear PtdIns(4,5)P2 synthesis in response to growth signals, which, in turn, promotes transcriptional changes [].
Transcription factor activator protein (AP)-1, comprising Jun (c-Jun, JunB, and JunD) and Fos (c-Fos, FosB, Fra1, and Fra2) family members, plays a central role in regulating gene transcription in various biological processes []. Fos protein family members form stable heterodimerswith Jun proteins and thereby enhance their DNAbindingactivity []. This entry reprsents fos-related antigen 2 (Fra2), which is implicated in TGFbeta signalling. Fra2 is a positive regulator of bone and matrix formation in mice and humans []. Fra2 is a STAT5 (signal transducers and activators of transcription 5) target gene regulated by IL-2 in human CD4 T cells []. It may also play an important role in the pathogenesis of systemic sclerosis, an autoimmune disease of unknown etiology that affects the skin and a variety of internal organs including the lungs, heart, and gastrointestinal tract [].
Basic leucine zipper transcriptional factor ATF-like 3 (B-ATF-3, also known as p21SNFT) is a AP-1 family transcription factor that can replace Fos in dimerisation with Jun on a consensus AP-1 binding site (12-O-tetradecanolyphorbol-13-acetate response element (TRE)) and interact with Jun and NF-AT at the distal NF-AT/AP-1 enhancer element []. It may repress transcriptional activity by inducing a unique conformation in the transcription factor complex [, ]. It controls the differentiation of CD8+ thymic conventional dendritic cells in the immune system [].
The transcription factor activator protein (AP)-1 consists of Jun (c-Jun, JunB, and JunD), Fos (c-Fos, FosB, Fra1, and Fra2), ATF (ATFa, ATF-2 and ATF-3) and JDP (JDP-1 and JDP-2) family members []. They are basic leucine zipper transcription factors that play a central role in regulating gene transcription in various biological processes []. This entry includes Jun family members. AP-1 proteins have a α-helical bZIP domain, which contains a basic DNA-binding region and regularly spaced leucine residues known as the leucine zipper motif []. They have similar protein structure and can either form homodimers or form heterodimers with other AP-1 proteins (predominantly with Jun proteins), which can then bind to TRE-like sequences (consensus sequence 5'-TGAG/CTCA-3') []. Each of these proteins are expressed in different tissues and can be regulated in different ways, which means that every cell type has a complex mixture of AP-1 dimers with subtly different functions [].
Transcription factor JunB is a member of the transcription factor activator protein (AP)-1 family, comprising Jun (c-Jun, JunB, and JunD), Fos (c-Fos, FosB, Fra1, and Fra2), ATF (ATFa, ATF-2 and ATF-3) and JDP (JDP-1 and JDP-2) family members []. They are basic leucine zipper transcription factors that play a central role in regulating gene transcription in various biological processes []. JunB may serve as a biomarkers for prognosis of breast cancer [].AP-1 proteins have a α-helical bZIP domain, which contains a basic DNA-binding region and regularly spaced leucine residues known as the leucine zipper motif []. They have similar protein structure and can either form homodimers or form heterodimers with other AP-1 proteins (predominantly with Jun proteins), which can then bind to TRE-like sequences (consensus sequence 5'-TGAG/CTCA-3') []. Each of these proteins are expressed in different tissues and can be regulated in different ways, which means that every cell type has a complex mixture of AP-1 dimers with subtly different functions [].
The transcription factor activator protein (AP)-1 consists of Jun (c-Jun, JunB, and JunD), Fos (c-Fos, FosB, Fra1, and Fra2), ATF and JDP family members []. They are basic leucine zipper transcription factors that play a central role in regulating gene transcription in various biological processes []. This entry includes Fos, ATF-3 and JDP family members. AP-1 proteins have a α-helical bZIP domain, which contains a basic DNA-binding region and regularly spaced leucine residues known as the leucine zipper motif []. They have similar protein structure and can either form homodimers or form heterodimers with other AP-1 proteins (predominantly with Jun proteins), which can then bind to TRE-like sequences (consensus sequence 5'-TGAG/CTCA-3') []. Each of these proteins are expressed in different tissues and can be regulated in different ways, which means that every cell type has a complex mixture of AP-1 dimers with subtly different functions [].
Transcription factor c-Jun (also known as transcription factor AP-1) is a member of the transcription factor activator protein (AP)-1 family, comprising Jun (c-Jun, JunB, and JunD), Fos (c-Fos, FosB, Fra1, and Fra2), ATF (ATFa, ATF-2 and ATF-3) and JDP (JDP-1 and JDP-2) family members []. They are basic leucine zipper transcription factors that play a central role in regulating gene transcription in various biological processes []. c-Jun was originally identified as the normal cellular counterpart of the viral Jun oncoprotein (v-Jun) encoded by an avian sarcoma virus (ASV17). The 39kDa c-Jun protein consists of a C-terminal basic region-leucine zipper (B-ZIP) DNA-binding domain and a N-terminal transcriptional activation domain.AP-1 proteins have a α-helical bZIP domain, which contains a basic DNA-binding region and regularly spaced leucine residues known as the leucine zipper motif []. They have similar protein structure and can either form homodimers or form heterodimers with other AP-1 proteins (predominantly with Jun proteins), which can then bind to TRE-like sequences (consensus sequence 5'-TGAG/CTCA-3') []. Each of these proteins are expressed in different tissues and can be regulated in different ways, which means that every cell type has a complex mixture of AP-1 dimers with subtly different functions [].
Transcription factor JunD is a member of the transcription factor activator protein (AP)-1 family, comprising Jun (c-Jun, JunB, and JunD), Fos (c-Fos, FosB, Fra1, and Fra2), ATF (ATFa, ATF-2 and ATF-3) and JDP (JDP-1 and JDP-2) family members []. They are basic leucine zipper transcription factors that play a central role in regulating gene transcription in various biological processes []. This entry also includes transcription factor AP-1 (Jra) from Drosophila, which recognizes and binds to the enhancer heptamer motif 5'-TGA[CG]TCA-3' and has a role in dorsal closure [, , ].AP-1 proteins have a α-helical bZIP domain, which contains a basic DNA-binding region and regularly spaced leucine residues known as the leucine zipper motif []. They have similar protein structure and can either form homodimers or form heterodimers with other AP-1 proteins (predominantly with Jun proteins), which can then bind to TRE-like sequences (consensus sequence 5'-TGAG/CTCA-3') []. Each of these proteins are expressed in different tissues and can be regulated in different ways, which means that every cell type has a complex mixture of AP-1 dimers with subtly different functions [].
The class III basic helix-turn-helix (bHLH) transcription factors have proliferative and apoptotic roles and are characterised by the presence of a leucine zipper adjacent to the bHLH domain. The myc oncogene was first discovered in small-cell lung cancer cell lines where it is found to be deregulated []. The Myc protein contains an N-terminal transcriptional regulatory domain followed by a nuclear localization signal and a C-terminal basic DNA binding domain tethered to a helix-loop-helix-leucine zipper (HLH-Zip) dimerization motif. Myc forms a heterodimer with Max, and this complex regulates cell growth through direct activation of genes involved in cell replication [, , ].The `leucine zipper' is a structure that is believed to mediate the function of several eukaryotic gene regulatory proteins. The zipper consists of a periodic repetition of leucine residues at every seventh position, and regions containing them appear to span eight turns of α-helix. The leucine side chains that extend from one helix interact with those from a similar helix, hence facilitating dimerisation in the form of a coiled-coil. Leucine zippers are present in many gene regulatory proteins, including the CREB proteins, Jun/AP1 transcription factors, fos oncogene and fos-related proteins, C-myc, L-myc and N-myc oncogenes, and so on.
Transcription initiation is dictated by the presence and activity of specific nuclear factors that bind to DNA regulatory sequences and interact with the transcriptional machinery. The functions of some of these factors can be altered by phosphorylation, which affects both DNA binding and transcriptional activation []. Phosphorylation is effected by specific protein kinases that have been activated by the stimulus of signal transduction pathways, resulting in the regulation of gene transcription by modulating the phosphorylation sites of transcription factors.Cyclic AMP (cAMP) regulates the expression of many genes via a conserved gene promoter element CRE (cAMP response element) [], which has the sequence 5'-TGACGTCA-3' []. The cAMP response element binding protein (CREB) is a nuclear factor that is regulated by protein kinase A phosphorylation. Transcription is stimulated on binding to the CRE of a phosphorylated CREB dimer, which is held together by leucine zippers. Dimerisation and transcriptional efficacy have been found to be stimulated by phosphorylation at several distinct sites, and it has thus been suggested []that CREB may be regulated by multiple kinases. Sequence analysis of the gene has revealed a cluster of protein kinase A, protein kinase C, and casein kinase II consensus recognition sites near the N terminus of the protein sequence, and the proximity of these sites to one another indicates the possibility of interaction in a positive or negative fashion to regulate CREB bioactivity.The 'leucine zipper' is a structure that is believed to mediate the function of several eukaryotic gene regulatory proteins. The zipper consists of a periodic repetition of leucine residues at every seventh position, and regions containing them appear to span 8 turns of α-helix. The leucine side chains that extend from one helix interact with those from a similar helix, hence facilitating dimerisation in the form of a coiled-coil. Leucine zippers are present in many gene regulatory proteins, including the CREB proteins, Jun/AP1 transcription factors, fos oncogene and fos-related proteins, C-myc, L-myc and N-myc oncogenes, and so on.
