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AMPK-sensed cellular energy state regulates the release of extracellular Fatty Acid Synthase.

Abstract：

:Fatty Acid Synthase (FASN), a 250-kDa cytosolic multi-enzyme catalyzing eukaryotic de novo FA biogenesis, unexpectedly localizes in cancer cell culture supernatants and in the blood of cancer patients. High levels of "extracellular FASN" have recently been found in supernatants from Hepatitis C Virus-infected liver cells. The ultimate mechanism regulating FASN release, however, remained completely undefined. When the AMPK-activating drug AICAR was used to simulate an elevated AMP/ATP ratio in breast cancer cells, ELISA-based analyses revealed that extracellular FASN dramatically augmented in a dose- and time-dependent manner. Immunoblotting procedures using a battery of anti-FASN antibodies further confirmed that, in response to AMPK activation, FASN protein is depleted from the cytosol to accumulate as different FASN isoforms in the extracellular milieu. siRNA-induced blockade of AMPK expression largely attenuated AICAR-promoted FASN release. FASN release might represent a previously unrecognized mechanism through which AMPK monitor and restores cellular energy state in response to increasing AMP/ATP ratios.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Oliveras-Ferraros C,Vazquez-Martin A,Fernández-Real JM,Menendez JA

doi

10.1016/j.bbrc.2008.11.067

subject

Has Abstract

pub_date

2009-01-16 00:00:00

pages

488-93

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(08)02264-X

journal_volume

378

pub_type

杂志文章

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