Identification and characterization of a novel GGA/C-binding protein, GBP-i, that is rapidly inducible by cytokines

Ganesh V. Raj, Kamel Khalili

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Immunosuppressive states with accompanying alterations in cytokine profiles have been postulated to play a vital role in the reactivation of viruses from latency. Cytokines regulate gene express by activating transcription factors via well-characterized signal transduction pathways. In this study, we report the identification of a novel inducible protein, GBP-i, that binds to a double-stranded GGA/C-rich region of the transcriptional control region of the human papovavirus JC virus (JCV), specifically within the origin of viral DNA replication. GBP-i is distinct from previously characterized GC-box-binding proteins with respect to both its sequence specificity and its electrophoretic mobility on native and denaturing gels. GBP-i responds within 90 min to phorbol myristate acetate stimulation; however, unlike typica phorbol myristate acetate-inducible factors, this rapid induction is regulated primarily at the transcriptional level. Further, the induction of GBP-i appears to be widespread and mediated by many inflammatory cytokines, including interleukin-1β, tumor necrosis factor alpha, gamma interferon, and transforming growth factor β. Interestingly, the induced protein acts as a transcriptional repressor in its native context in the JCVL promoter. However, when its binding sequence is transposed to a heterologous promoter, GBP-i appears to function as a transcriptional activator. The data presented here suggest a role for GBP-i in cytokine-mediated induction of viral and cellular genes.

Original languageEnglish (US)
Pages (from-to)7770-7781
Number of pages12
JournalMolecular and Cellular Biology
Volume14
Issue number12
StatePublished - Dec 1994

Fingerprint

Carrier Proteins
Cytokines
Tetradecanoylphorbol Acetate
Activating Transcription Factors
JC Virus
Virus Latency
Viral Genes
Viral DNA
Transforming Growth Factors
Immunosuppressive Agents
DNA Replication
Interleukin-1
Interferon-alpha
Interferon-gamma
Signal Transduction
Proteins
Tumor Necrosis Factor-alpha
Gels
Genes

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

Cite this

Identification and characterization of a novel GGA/C-binding protein, GBP-i, that is rapidly inducible by cytokines. / Raj, Ganesh V.; Khalili, Kamel.

In: Molecular and Cellular Biology, Vol. 14, No. 12, 12.1994, p. 7770-7781.

Research output: Contribution to journalArticle

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