Methylation-controlled J protein promotes c-Jun degradation to prevent ABCB1 transporter expression.

Abstract:

:Methylation-controlled J protein (MCJ) is a newly identified member of the DnaJ family of cochaperones. Hypermethylation-mediated transcriptional silencing of the MCJ gene has been associated with increased chemotherapeutic resistance in ovarian cancer. However, the biology and function of MCJ remain unknown. Here we show that MCJ is a type II transmembrane cochaperone localized in the Golgi network and present only in vertebrates. MCJ is expressed in drug-sensitive breast cancer cells but not in multidrug-resistant cells. The inhibition of MCJ expression increases resistance to specific drugs by inducing expression of the ABCB1 drug transporter that prevents intracellular drug accumulation. The induction of ABCB1 gene expression is mediated by increased levels of c-Jun due to an impaired degradation of this transcription factor in the absence of MCJ. Thus, MCJ is required in these cells to prevent c-Jun-mediated expression of ABCB1 and maintain drug response.

journal_name

Mol Cell Biol

authors

Hatle KM,Neveu W,Dienz O,Rymarchyk S,Barrantes R,Hale S,Farley N,Lounsbury KM,Bond JP,Taatjes D,Rincón M

doi

10.1128/MCB.01804-06

subject

Has Abstract

pub_date

2007-04-01 00:00:00

pages

2952-66

issue

8

eissn

0270-7306

issn

1098-5549

pii

MCB.01804-06

journal_volume

27

pub_type

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