Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepadnaviruses, as well as other pararetroviruses, express their pol (P) gene product unfused to the preceding core gene implying that these retroelements have developed a mechanism for initiating assembly and replication that is principally different from the one used by retroviruses and retrotransposons. We have analysed this mechanism for the human hepatitis B virus by using a newly developed, highly sensitive detection method based upon radiolabelling of the P protein at newly introduced target sites for protein kinase A. The results obtained demonstrate that polymerase encapsidation depends on the concomittant encapsidation of the HBV RNA pregenome and that packaging of the viral RNA, in turn, depends on the presence of P protein. Loss of P protein encapsidation by mutations inactivating the HBV RNA encapsidation signal epsilon could be compensated by trans-complementation with recombinant RNA molecules carrying the epsilon sequence. Thus, in contrast to retroviral replication, the interaction of the hepadnaviral P protein and the RNA genome at its packaging signal appears to be crucial for initiating the formation of replication-competent nucleocapsids. Furthermore, RNA control of P protein packaging stringently limits the number of polymerase molecules that can be encapsidated.
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PMID:Hepadnaviral assembly is initiated by polymerase binding to the encapsidation signal in the viral RNA genome. 138 Apr 55

DNA beta-polymerase (beta-pol), one of the recognized DNA polymerizing enzymes in vertebrates, has a role in 'very short patch' gap-filling synthesis during nucleotide excision DNA repair. In human and mouse, the enzyme is encoded by a single-copy gene located on the short arm of chromosome 8 near the centromere. In a series of studies, we have found that the cloned human beta-pol promoter is regulated by signals acting through the single ATF/CRE palindrome in the core promoter. These signals include transactivation by: adenovirus E1a/E1b proteins; activated p21ras; and in CHO cells, treatment with the DNA damaging agent MNNG. Hence, several types of stimulatory signals are mediated through the single ATF/CRE site, including DNA damage induction. To understand the mechanism of beta-pol promoter activation by MNNG in CHO cells, we asked whether induction of the cAMP/protein kinase A pathway can increase transcription of the cloned promoter in this system. Agents that increase cellular cAMP levels (8-BrcAMP; forskolin and IBMx) activated the beta-pol promoter fusion gene in transient expression experiments, and a mutation in the ATF/CRE palindrome blocked this response. Thus, the ATF/CRE site appears to be cAMP responsive in the CHO cell system. We found that the activation of the cloned beta-pol promoter by MNNG does not occur with two mutant CHO cell lines that are deficient in protein kinase A activity. Further, simultaneous treatment of wild-type CHO cells, with MNNG and to elevate cAMP, failed to result in an additive effect for activation of the beta-pol promoter. Thus, these effectors may act through a common pathway. These results suggest that the activation of the cloned beta-pol promoter in CHO cells following MNNG treatment is mediated through the cAMP/protein kinase A signal transduction pathway.
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PMID:DNA damage response of cloned DNA beta-polymerase promoter is blocked in mutant cell lines deficient in protein kinase A. 145 16

UBF is a DNA binding protein which interacts with both the promoter and the enhancer of various vertebrate ribosomal RNA genes and functions as a transcription initiation factor for RNA polymerase I (pol I). We have purified murine UBF to apparent molecular homogeneity and demonstrate that its transactivating potential, but not its DNA binding activity, is modulated in response to cell growth. In vivo labelling experiments demonstrate that UBF is a phosphoprotein and that the phosphorylation state is different in growing and quiescent cells. We show that UBF is phosphorylated in vitro by a cellular protein kinase which by several criteria closely resembles casein kinase II (CKII). A major modification involves serine phosphoesterifications in the carboxy terminal hyperacidic tail of UBF. Deletions of this C-terminal domain severely decreases the UBF directed activation of transcription. The data suggest that phosphorylation of UBF by CKII may play an important role in growth dependent control of rRNA synthesis.
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PMID:The nucleolar transcription factor mUBF is phosphorylated by casein kinase II in the C-terminal hyperacidic tail which is essential for transactivation. 160 Sep 46

The gene for the mammalian DNA repair enzyme DNA polymerase beta (beta-pol) is constitutively expressed in most cells, but is regulated in a tissue-specific fashion and can be induced in response to some types of DNA damaging agents. The promoter for the human beta-pol gene has been characterized and found to be TATA-less, but it does have multiple GC boxes and one ATF/CRE-binding site located within 50 residues 5' of the major mRNA start site. The ATF/CRE-binding site has been found to be essential for activity of the cloned promoter. We report that a bovine testes DNA-binding protein with specificity for the beta-pol promoter ATF/CRE-binding site is phosphorylated in vivo and contains several phosphorylation sites. Sequence specific DNA-binding by the purified protein is reduced when the natural protein is dephosphorylated or when it is hyperphosphorylated by protein kinase A (cKA) in vitro. These results suggest the possibility that phosphorylation systems may change binding of this ATF/CRE-binding protein to the beta-pol promoter and in turn modulate the promoter. Possible correlation of the results with transient expression activity of the cloned beta-pol promoter fusion gene was obtained in 293 cells. Cotransfection with a cKA expression plasmid to elevate phosphorylation was found to strongly reduce promoter activity.
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PMID:Mammalian beta-polymerase promoter: phosphorylation of ATF/CRE-binding protein and regulation of DNA binding. 182 17

Faithful and efficient transcription initiation at the mouse ribosomal gene promoter requires besides RNA polymerase I (pol I) four polypeptide trans-acting factors, termed TIF-IA, TIF-IB, TIF-IC, and mUBF. We have partially purified these proteins from cultured Ehrlich ascites cells and show that in the presence of TIF-IA and TIF-IB, pol I directs very low amounts of specific transcripts. Neither TIF-IC nor mUBF on their own significantly stimulate the efficiency of template utilization. However, both factors together strongly activate transcription. Interestingly, factor TIF-IB - the murine homologue of human SL1 - fails to program a human extract to transcribe the murine template, but requires its homologous RNA polymerase I. This finding implicates that not only some rDNA transcription factors but also pol I exhibits species-specific differences. The growth-related factor TIF-IA, on the other hand, stimulates both mouse and human rDNA transcription. This regulatory factor whose amount or activity fluctuates according to the proliferation rate of the cells, is functionally inactivated by antibodies against cdc2 protein kinase. This result together with the observation that transcription is stimulated by ATP-gamma S, an ATP analogue which is a substrate for protein kinases but not for protein phosphatases, strongly suggests that post-translational protein modification is involved in rDNA transcription regulation.
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PMID:Trans-acting factors involved in species-specificity and control of mouse ribosomal gene transcription. 192 92

A new avian transforming retrovirus, NK24, was isolated from a chicken with a nephroblastoma. This transforming virus induced fibrosarcomas with osteogenic cell proliferation and nephroblastomas in vivo and transformed fibroblast cells in vitro. From extracts of NK24-transformed cells, anti-gag serum immunoprecipitated a 100-kilodalton nonglycosylated protein with no detectable protein kinase activity. An NK24 provirus present in infected quail cells was molecularly cloned and subjected to nucleotide sequence analysis. The genome of NK24 was 5.3 kilobases long and had a 1,126-base-pair sequence of cellular origin in place of a viral sequence of avian leukosis virus containing the 3' half of the gag gene and the 5' half of the pol gene. Although the entire env gene was retained, it appeared to be inactive, possibly owing to the loss of function of its splice acceptor site as a result of a second deletion of 1,598 bases in the 3' half of the pol gene that extended to the acceptor site. Nucleotide sequence analysis revealed that the NK24 virus contained the fos gene, previously identified as the oncogene of FBJ and FBR murine osteosarcoma viruses. Unlike the v-fos gene products of FBJ and FBR, which suffer a structural alteration at their carboxyl termini, the NK24 v-fos gene product seemed to have the same carboxyl-terminal structure as the chicken c-fos gene product. A comparison of the structures of the products of the NK24 v-fos and mouse c-fos genes suggested that the fos gene product consists of highly conserved regions and relatively divergent regions.
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PMID:An avian transforming retrovirus isolated from a nephroblastoma that carries the fos gene as the oncogene. 282 11

The HZ2-feline sarcoma virus (HZ2-FeSV) is a replication-defective acute transforming feline retrovirus with oncogene homology to Abelson murine leukemia virus (A-MuLV) (P. Besmer, W.D. Hardy,Jr., E. E. Zuckerman, P. J. Bergold, L. Lederman, and H. W. Snyder, Jr. (1983) Nature (London) 303, 825-828). In contrast to A-MuLV which was isolated from a hematopoietic tumor, the HZ2-FeSV derives from a multicentric fibrosarcoma. We have molecularly cloned the HZ2-FeSV provirus from mink HZ2-FeSV nonproducer cells. The molecularly cloned HZ2-FeSV provirus is biologically active upon transfection of NIH 3T3 indicator cells. The genetic structure of the HZ2-FeSV provirus was determined by EM heteroduplex and Southern blot analysis. The HZ2-FeSV has a 6.8 kb-viral genome with the structure: 5' delta gag-abl-delta pol-delta env 3'. The abl insert, which is 1.4 kb, is located 1.9 kb from the 5' end and 3.5 kb from the 3' end of the viral genome. The 5' 1.9 kb in the HZ2-FeSV are colinear with 5' FeLV sequences, and the 3' 3.5 kb are colinear with 3' FeLV sequences, with the exception of a 0.85-kb deletion in the env gene. HZ2-FeSV v-abl and A-MuLV v-abl share 1.2 kb of abl sequences which are known to specify the protein kinase domain of the abl gene product and are necessary for fibroblast transformation in vitro. The DNA from several tumor tissues of cat 3590 from which the HZ2-FeSV was obtained was found to contain several HZ2-FeSV-related proviruses including the HZ2-FeSV. The variant HZ2-FeSVs have indistinguishable 5' gag-abl sequences; however, they differ in 3' sequences which likely do not include any abl sequences. The DNAs from fibrosarcomas obtained by inoculation of kittens with tumor extract were found to contain variant HZ2-FeSV proviruses as well. Taken together these results indicate a role for the HZ2-FeSVs in sarcomagenesis.
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PMID:Structure and origins of the HZ2-feline sarcoma virus. 288 77

A new acute transforming feline retrovirus, the Hardy-Zuckerman 4 feline sarcoma virus (HZ4-FeSV), has been isolated from a feline fibrosarcoma. The viral genome of HZ4-FeSV contains a new oncogene designated v-kit, has the structure 5' delta gag-kit-delta pol-delta env 3' and specifies a gag-kit polyprotein of relative molecular mass 80,000. The predicted kit amino-acid sequence displays partial homology with tyrosine-specific protein kinase oncogenes. HZ4-FeSV appears to have been generated by transduction of feline c-kit sequences with feline leukaemia virus.
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PMID:A new acute transforming feline retrovirus and relationship of its oncogene v-kit with the protein kinase gene family. 300 97

Hardy-Zuckerman 2 feline sarcoma virus (HZ2-FeSV), isolated from a multicentric feline fibrosarcoma is a replication-defective acute transforming feline retrovirus which originated by transduction of feline c-abl sequences with feline leukemia virus (FeLV) and is known to encode a 110-kilodalton gag-abl fusion protein with tyrosine-specific protein kinase activity (P. Besmer, W. D. Hardy, E. E. Zuckerman, P. J. Bergold, L. Lederman, and H. W. Snyder, Nature (London) 303:825-828, 1983). The nucleotide sequence of the abl segment in the HZ2-FeSV genome was determined and compared with the murine and human v-abl and c-abl sequences. The predicted transforming protein consists of 344 amino acids (aa) of FeLV gag origin, 439 aa of abl origin, and at least 200 aa of FeLV pol origin (p110gag-abl-pol). The 1,317-base-pair HZ2-FeSV v-abl segment (fv-abl) corresponds to 5' abl sequences which include the region known to specify the protein kinase domain. The 5' 189 base pairs of fv-abl correspond to 5' c-abl sequences not contained in Abelson murine leukemia virus (MuLV) v-abl. The mouse c-abl exon which contains these segments was identified, and its nucleotide sequence was determined. Comparison of the predicted amino acid sequence of fv-abl with those of Abelson MuLV v-abl and c-abl revealed five aa differences. The 5' junction between FeLV and abl was found to involve a preferred region in FeLV gag p30 (P. Besmer, J. E. Murphy, P. C. George, F. H. Qiu, P. J. Bergold, L. Lederman, H. W. Snyder, D. Brodeur, E. E. Zuckerman, and W. D. Hardy, Nature (London) 320:415-421, 1986). A six-base homology exists at the recombination site between the parental FeLV and the c-abl sequences. The 3' junction between fv-abl and FeLV pol predicts an in-frame fusion of fv-abl and FeLV pol. A transformed cell line containing a truncated gag-abl-pol protein, p85, that lacks most of the FeLV pol sequences was obtained by transfection of NIH 3T3 mouse cells. This result implies that the pol sequences of the p110gag-abl-pol protein are dispensable for fibroblast transformation. To assess whether the fv-abl segment specifies the unique biological properties of HZ2-FeSV, we constructed a Moloney MuLV-based version of HZ2-FeSV, Mo-MuLV(fv-abl), in which the fv-abl sequences were contained in a genetic context similar to that in HZ2-FeSV.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Nucleic acid sequence and oncogenic properties of the HZ2 feline sarcoma virus v-abl insert. 302 15

Two replication-defective avian sarcoma viruses, S1 and S2, which were independently isolated from tumors of chickens inoculated with avian lymphatic leukosis virus (LLV) were characterized. The genomes of S1 and S2 contain src-related sequences and are, respectively, about 3.9 and 4.5 kilobases long. pp60src-related proteins with molecular weights of 62,000 (p62) were detected in cells infected with these viruses, and protein kinase activity was found to be associated with these proteins. No other viral proteins, such as gag, pol, and env gene products, were detected. These results suggested that the c-src sequence in normal chicken cells was incorporated into LLV genomes by recombination at the expense of most of the viral genes to generate highly defective new sarcoma viruses.
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PMID:Characterization of two strains of avian sarcoma virus isolated from avian lymphatic leukosis virus-induced sarcomas. 609 28


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