Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In regenerating liver, a physiologically normal model of cell growth, LRF-1, JunB, c-Jun, and c-Fos among Jun/Fos/LRF-1 family members are induced posthepatectomy. In liver cells, high levels of c-Fos/c-Jun, c-Fos/JunB, LRF-1/c-Jun, and LRF-1/JunB complexes are present for several hours after the G0/G1 transition, and the relative level of LRF-1/JunB complexes increases during G1. We provide evidence for dramatic differences in promoter-specific activation by LRF-1- and c-Fos-containing complexes. LRF-1 in combination with either Jun protein strongly activates a cyclic AMP response element-containing promoter which c-Fos/Jun does not activate. LRF-1/c-Jun, c-Fos/c-Jun, and c-Fos/JunB activate specific AP-1 and ATF site-containing promoters, and in contrast, LRF-1/JunB potently represses c-Fos- and c-Jun-mediated activation of these promoters. Repression is dependent on a region in LRF-1 that includes amino acids 40 to 84 (domain R) and the basic/leucine zipper domain. As the relative level of LRF-1/JunB complexes increases posthepatectomy, c-Fos/Jun-mediated ATF and AP-1 site activation is likely to decrease with simultaneous transcriptional activation of the many liver-specific genes whose promoters contain cyclic AMP response element sites. Thus, through complex interactions among LRF-1, JunB, c-Jun, and c-Fos, control of delayed gene expression may be established for extended times during the G1 phase of hepatic growth.
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PMID:Interactions among LRF-1, JunB, c-Jun, and c-Fos define a regulatory program in the G1 phase of liver regeneration. 140 55

Liver regeneration provides one of the few systems for analysis of mitogenesis in the fully developed, intact animal. Several proteins have been identified as part of the primary growth response in regenerating liver and in mitogen-stimulated cells. Some of these proteins, such as the Jun and Fos families of transcription factors, are thought to have a role in activating transcription of genes expressed subsequently in the growth response. Through differential screening of a regenerating-liver cDNA library, we have identified a rapidly and highly induced gene encoding a 21-kDa leucine-zipper-containing protein that we have designated liver regeneration factor 1 (LRF-1). LRF-1 has no homology with other leucine-zipper proteins outside the basic and leucine-zipper domains. LRF-1 alone can bind DNA, but it preferentially forms heteromeric complexes with c-Jun and Jun-B and does not interact with c-Fos. In solution, it binds with highest affinity to cAMP response elements but also has affinity for related sites. In cotransfection studies, LRF-1 in combination with c-Jun strongly activates a c-Jun-responsive promoter. The induction of the LRF-1 gene in regenerating liver greatly increases the potential variety of heterodimeric combinations of leucine-zipper transcription factors. While LRF-1 mRNA is rapidly induced in the absence of protein synthesis, its peak induction is later than c-fos mRNA, suggesting that LRF-1 may regulate responsive genes at a later point in the cell cycle. As such, LRF-1 may have a unique and critical role in growth regulation of regenerating liver and mitogen-stimulated cells.
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PMID:Identification of LRF-1, a leucine-zipper protein that is rapidly and highly induced in regenerating liver. 190 65

Nuclear levels of c-Jun, JunB, c-Fos, and LRF-1 (liver regeneration factor) are high for a large fraction of the G1 phase in regenerating liver and mitogen-stimulated hepatic cells. Previously, JunB was regarded as a less potent transcriptional activator than c-Jun that could also function as a repressor. However, we found that, like c-Jun, JunB alone or LRF-1/JunB strongly transactivates a cAMP-responsive promoter. Unlike c-Jun, JunB represses several AP-1 or activator of transcription factor site-containing promoters, and this inhibition is greatly enhanced in the presence of LRF-1. Here, we identify separate regions of JunB required for trans-activation and repression of these promoters. Deletion analysis shows that the region involved in trans-activation function is highly conserved among all Jun family members and corresponds to activator domain (A1) of c-Jun. In contrast, repression is maximal in the presence of both the DNA-binding domain and a region proximal to the basic region that is highly divergent among Jun proteins. Functional distinctions between Jun proteins during induction of the growth response and tumorigenesis may be accounted for by promoter-specific activation and repression mediated by regional differences in Jun family proteins.
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PMID:Promoter-specific trans-activation and inhibition mediated by JunB. 833 92

To study macrophage genes activated by lipopolysaccharide (LPS) we have constructed a cDNA library using the mouse macrophage cell line, RAW 264.7. By differential screening, a gene, designated LRG-21, was identified that showed nucleic acid sequence homology to rat liver regenerating factor-1 (LRF-1) and human activating transcription factor-3 (ATF3). Both LRG-21 and LRF-1 are transcribed within an hour following stimulation and in the absence of protein synthesis. The predicted protein sequence of LRG-21 consists of 181 amino acids with a molecular weight of 20.7 kDa. All three sequences contain basic and leucine zipper regions characteristic of the c-Fos and c-Jun family of transcription factors, but the remainder of the sequences are unrelated to this family. Recombinant LRG-21 has been shown to bind to a phorbol ester promoter element. Additional experiments have shown that LRG-21 is also induced by interferon-gamma (IFN-gamma) and by interleukin-4 (IL-4) in both RAW264.7 cells and murine peritoneal macrophages. Based on these observations, it is likely that LRG-21 plays an important role in macrophage activation.
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PMID:Identification of a lipopolysaccharide inducible transcription factor in murine macrophages. 896 Jan 23