Cell Cycle-coupled Variation in Topoisomerase II alpha mRNA Is Regulated by the 3'-Untranslated Region. Possible role of redox-sensitive protein binding in mRNA accumulation

Prabhat C Goswami; Jamie Sheren; Lee D Albee; Azemat Parsian; Julia E Sim; Lisa A Ridnour; Ryuji Higashikubo; David Gius; Clayton R Hunt; Douglas R Spitz

doi:10.1074/jbc.M005298200

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Cell Cycle-coupled Variation in Topoisomerase II alpha mRNA Is Regulated by the 3'-Untranslated Region. Possible role of redox-sensitive protein binding in mRNA accumulation

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Cell Cycle-coupled Variation in Topoisomerase II alpha mRNA Is Regulated by the 3'-Untranslated Region. Possible role of redox-sensitive protein binding in mRNA accumulation

Prabhat C Goswami, Jamie Sheren, Lee D Albee, Azemat Parsian, Julia E Sim, Lisa A Ridnour, Ryuji Higashikubo, David Gius, Clayton R Hunt and Douglas R Spitz

The Journal of biological chemistry, Vol.275(49), pp.38384-38392

12/08/2000

DOI: 10.1074/jbc.M005298200

PMID: 10986283

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Abstract

Mammalian topoisomerase II alpha (Topo II) is a highly regulated enzyme essential for many cellular processes including the G sub(2) cell cycle checkpoint. Because Topo II gene expression is regulated posttranscriptionally during the cell cycle, we investigated the possible role of the 3'-untranslated region (3'-UTR) in controlling Topo II mRNA accumulation. Reporter assays in stably transfected cells demonstrated that, similar to endogenous Topo II mRNA levels, the mRNA levels of reporter genes containing the Topo II 3'-UTR varied during the cell cycle and were maximal in S and G sub(2)/M relative to G sub(1). Topo II 3'-UTR sequence analysis and RNA-protein binding assays identified a 177- nucleotide (base pairs 4772-4949) region containing an AUUUUUA motif sufficient for protein binding. Multiple proteins (84, 70, 44, and 37 kDa) bound this region, and the binding of 84- and 37-kDa (tentatively identified as the adenosine- or uridine-rich element-binding factor AUF1) proteins was enhanced in G sub(1), correlating with decreased Topo II mRNA levels. The binding activity was enhanced in cellular extracts or cells treated with thiol-reducing agents, and increased binding correlated with decreased Topo II mRNA levels. These results support the hypothesis that cell cycle-coupled Topo II gene expression is regulated by interaction of the 3'-UTR with redox-sensitive protein complexes.

AUF1 protein

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Title: Subtitle: Cell Cycle-coupled Variation in Topoisomerase II alpha mRNA Is Regulated by the 3'-Untranslated Region. Possible role of redox-sensitive protein binding in mRNA accumulation
Creators: Prabhat C Goswami
Jamie Sheren
Lee D Albee
Azemat Parsian
Julia E Sim
Lisa A Ridnour
Ryuji Higashikubo
David Gius
Clayton R Hunt
Douglas R Spitz
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.275(49), pp.38384-38392
DOI: 10.1074/jbc.M005298200
PMID: 10986283
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Language: English
Date published: 12/08/2000
Academic Unit: Pathology; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center
Record Identifier: 9984047993502771

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