Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nucleolar transcription factor UBF consists of two proteins, UBF1 and UBF2, which originate by alternative splicing. Here we show that deletion of 37 amino acids within the second of five HMG box motifs in UBF2 is important for the dual role of UBF as transcriptional activator and antirepressor. UBF1 is a potent antirepressor and transcriptional activator, whereas the ability of UBF2 to counteract histone H1-mediated repression and to stimulate ribosomal gene transcription both in vivo and in vitro is at least one order of magnitude lower. The difference in transcriptional activity between UBF1 and UBF2 is due to their different binding to the ribosomal gene promoter and enhancer. Apparently, the presence of an intact HMG box2 modulates the sequence-specific binding of UBF to rDNA control elements. However, the interaction of UBF with rDNA does not entirely depend on sequence recognition. Both UBF isoforms bind efficiently to four-way junction DNA, indicating that they recognize defined DNA structures rather than specific sequences. The results demonstrate that the HMG boxes are functionally diverse and that HMG box2 plays an important role in specific binding of UBF to rDNA.
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PMID:Functional differences between the two splice variants of the nucleolar transcription factor UBF: the second HMG box determines specificity of DNA binding and transcriptional activity. 831 87

The tumor suppressor protein p53 is frequently inactivated in tumors. It functions as a transcriptional activator as well as a repressor for a number of viral and cellular promoters transcribed by RNA polymerase II (Pol II) and by RNA Pol III. Moreover, it appears that p53 also suppresses RNA Pol I transcription. In this study, we examined the molecular mechanism of Pol I transcriptional inhibition by p53. We show that wild-type, but not mutant, p53 can repress Pol I transcription from a human rRNA gene promoter in cotransfection assays. Furthermore, we show that recombinant p53 inhibits rRNA transcription in a cell-free transcription system. In agreement with these results, p53-null epithelial cells display an increased Pol I transcriptional activity compared to that of epithelial cells that express p53. However, both cell lines display comparable Pol I factor protein levels. Our biochemical analysis shows that p53 prevents the interaction between SL1 and UBF. Protein-protein interaction assays indicate that p53 binds to SL1, and this interaction is mostly mediated by direct contacts with TATA-binding protein and TAF(I)110. Moreover, template commitment assays show that while the formation of a UBF-SL1 complex can partially relieve the inhibition of transcription, only the assembly of a UBF-SL1-Pol I initiation complex on the rDNA promoter confers substantial protection against p53 inhibition. In summary, our results suggest that p53 represses RNA Pol I transcription by directly interfering with the assembly of a productive transcriptional machinery on the rRNA promoter.
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PMID:Repression of RNA polymerase I transcription by the tumor suppressor p53. 1091 76

The replication cycle of human cytomegalovirus (CMV) leads to drastic reorganization of domains in the host cell nucleus. However, the mechanisms involved and how these domains contribute to infection are not well understood. Our recent studies defining the CMV-induced nuclear proteome identified several viral proteins of unknown functions, including a protein encoded by the UL31 gene. We set out to define the role of UL31 in CMV replication. UL31 is predicted to encode a 74-kDa protein, referred to as pUL31, containing a bipartite nuclear localization signal, an intrinsically disordered region overlapping arginine-rich motifs, and a C-terminal dUTPase-like structure. We observed that pUL31 is expressed with true late kinetics and is localized to nucleolin-containing nuclear domains. However, pUL31 is excluded from the viral nuclear replication center. Nucleolin is a marker of nucleoli, which are membrane-less regions involved in regulating ribosome biosynthesis and cellular stress responses. Other CMV proteins associate with nucleoli, and we demonstrate that pUL31 specifically interacts with the viral protein, pUL76. Coexpression of both proteins altered pUL31 localization and nucleolar organization. During infection, pUL31 colocalizes with nucleolin but not the transcriptional activator, UBF. In the absence of pUL31, CMV fails to reorganize nucleolin and UBF and exhibits a replication defect at a low multiplicity of infection. Finally, we observed that pUL31 is necessary and sufficient to reduce pre-rRNA levels, and this was dependent on the dUTPase-like motif in pUL31. Our studies demonstrate that CMV pUL31 functions in regulating nucleolar biology and contributes to the reorganization of nucleoli during infection.IMPORTANCE Nucleolar biology is important during CMV infection with the nucleolar protein, with nucleolin playing a role in maintaining the architecture of the viral nuclear replication center. However, the extent of CMV-mediated regulation of nucleolar biology is not well established. Proteins within nucleoli regulate ribosome biosynthesis and p53-dependent cellular stress responses that are capable of inducing cell cycle arrest and/or apoptosis, and they are proposed targets for cancer therapies. This study establishes that CMV protein pUL31 is necessary and sufficient to regulate nucleolar biology involving the reorganization of nucleolar proteins. Understanding these processes will help define approaches to stimulate cellular intrinsic stress responses that are capable of inhibiting CMV infection.
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PMID:Cytomegalovirus Late Protein pUL31 Alters Pre-rRNA Expression and Nuclear Organization during Infection. 2865 85