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PMID:18035482

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Citation

Sun, Y, Qiao, L, Xia, HH, Lin, MC, Zou, B, Yuan, Y, Zhu, S, Gu, Q, Cheung, TK, Kung, HF, Yuen, MF, Chan, AO and Wong, BC (2008) Regulation of XAF1 expression in human colon cancer cell by interferon beta: activation by the transcription regulator STAT1. Cancer Lett. 260:62-71

Abstract

XIAP-associated factor 1 (XAF1) is a novel tumor suppressor and interferon stimulated gene (ISG). Interferon beta (IFNbeta) exerts anti-proliferative effect and induces apoptosis through the Jak-Stat signaling cascade by the type I Interferon receptor (IFN-R), which initiates gene transcription of those biological effectors of IFNbeta. The aim of this study is to determine the effect of IFNbeta on XAF1 expression and the putative mechanisms mediated by the critical role of signal transducers and activators of transcription 1 (Stat1). Gene expression was detected by RT-PCR and Western blot analysis. The promoter activity of XAF1 was examined by luciferase reporter assay. The activity of interferon stimulated response element (ISRE) was assessed by electrophoretic mobility shift assay (EMSA) and quantitative chromatin immunoprecipitation assay (Q-ChIP). Results showed that IFNbeta stimulated XAF1 promoter activity in colon cancer cell line DLD1 in a time- and dose-dependent manner. A high affinity ISRE binding element (ISRE-XAF1) was located in -55 to -66 nt upstream of the first ATG site of XAF1 gene. Deletion of ISRE-XAF1 completely abrogated basal and IFNbeta-induced promoter activity. IFNbeta-induced XAF1 expression was mediated by Stat1 through the interaction with ISRE-XAF1. Knocking down of the Stat1 expression and blocking its phosphorylation decreased IFNbeta-induced XAF1 expression. Results suggested that induction of an immediate early response gene-XAF1 by IFNbeta was mediated by the transcription regulator Stat1 through the ISRE site within the promoter region of XAF1 gene in colon cancer.

Links

PubMed Online version:10.1016/j.canlet.2007.10.014

Keywords

Base Sequence; Cell Line, Tumor; Colonic Neoplasms/genetics; Colonic Neoplasms/metabolism; Colonic Neoplasms/pathology; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; Humans; Interferon Regulatory Factor-1/metabolism; Interferon-beta/metabolism; Interferon-beta/pharmacology; Intracellular Signaling Peptides and Proteins; Molecular Sequence Data; Neoplasm Proteins/genetics; Neoplasm Proteins/metabolism; Phosphorylation; Promoter Regions, Genetic; RNA Interference; RNA, Messenger/metabolism; RNA, Small Interfering/metabolism; Recombinant Proteins/metabolism; Response Elements; STAT1 Transcription Factor/metabolism; Signal Transduction/drug effects; Time Factors; Transcription, Genetic; Transfection; Up-Regulation

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:IFNB

involved_in

GO:0033141: positive regulation of peptidyl-serine phosphorylation of STAT protein

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IFNB

involved_in

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IRF1

located_in

GO:0000785: chromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:IRF1

enables

GO:0000978: RNA polymerase II cis-regulatory region sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_at:(SO:0000167)

Seeded From UniProt

complete

HUMAN:IRF1

involved_in

GO:0035458: cellular response to interferon-beta

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:STAT1

located_in

GO:0000785: chromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:STAT1

enables

GO:0000978: RNA polymerase II cis-regulatory region sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_at:(SO:0000167)

Seeded From UniProt

complete

HUMAN:STAT1

involved_in

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:STAT1

involved_in

GO:0035458: cellular response to interferon-beta

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:XAF1

involved_in

GO:0035456: response to interferon-beta

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IFNB

involved_in

GO:0060337: type I interferon signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IFNB

involved_in

GO:0035458: cellular response to interferon-beta

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IFNB

involved_in

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_regulation_target:(UniProtKB:Q6GPH4)
  • part_of:(GO:0035458)|has_regulation_target(UniProtKB:Q6GPH4)
  • part_of:(GO:0060337)

Seeded From UniProt

complete

HUMAN:IFNB

involved_in

GO:0033141: positive regulation of peptidyl-serine phosphorylation of STAT protein

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_regulation_target:(UniProtKB:P42224)
  • part_of:(GO:0035458)|has_regulation_target(UniProtKB:P42224)
  • part_of:(GO:0060337)

Seeded From UniProt

complete

See also

References

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