EMAIL THIS PAGE TO A FRIEND

Molecular endocrinology (Baltimore, Md.)

USP7 attenuates hepatic gluconeogenesis through modulation of FoxO1 gene promoter occupancy.


PMID 24694308

Abstract

Hepatic forkhead protein FoxO1 is a key component of systemic glucose homeostasis via its ability to regulate the transcription of rate-limiting enzymes in gluconeogenesis. Important in the regulation of FoxO1 transcriptional activity are the modifying/demodifying enzymes that lead to posttranslational modification. Here, we demonstrate the functional interaction and regulation of FoxO1 by herpesvirus-associated ubiquitin-specific protease 7 (USP7; also known as herpesvirus-associated ubiquitin-specific protease, HAUSP), a deubiquitinating enzyme. We show that USP7-mediated mono-deubiquitination of FoxO1 results in suppression of FoxO1 transcriptional activity through decreased FoxO1 occupancy on the promoters of gluconeogenic genes. Knockdown of USP7 in primary hepatocytes leads to increased expression of FoxO1-target gluconeogenic genes and elevated glucose production. Consistent with this, USP7 gain-of-function suppresses the fasting/cAMP-induced activation of gluconeogenic genes in hepatocyte cells and in mouse liver, resulting in decreased hepatic glucose production. Notably, we show that the effects of USP7 on hepatic glucose metabolism depend on FoxO1. Together, these results place FoxO1 under the intimate regulation of deubiquitination and glucose metabolic control with important implication in diseases such as diabetes.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

SAB2502100
Anti-LMNB1 antibody produced in goat, affinity isolated antibody, buffered aqueous solution
SAB2502101
Anti-LMNB1 antibody produced in goat, affinity isolated antibody, buffered aqueous solution
SAB2101352
Anti-LMNB1 antibody produced in rabbit, affinity isolated antibody
SAB1410759
Anti-LMNB1 antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
SAB1306823
ANTI-USP7 (CENTER) antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
HPA015641
Anti-USP7 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB2900786
Anti-USP7 antibody produced in rabbit, affinity isolated antibody
PLA0306
Goat anti-USP7 Antibody, Affinity Purified, Powered by Bethyl Laboratories, Inc.
SAB1400153
Monoclonal Anti-LMNB1 antibody produced in mouse, clone 4B10, purified immunoglobulin, buffered aqueous solution
SAB1404027
Monoclonal Anti-LMNB1 antibody produced in mouse, clone 4E4, purified immunoglobulin, buffered aqueous solution
SAB5300358
Monoclonal Anti-USP7 antibody produced in mouse, clone 5F11, ascites fluid
SAB4200042
Monoclonal Anti-USP7 antibody produced in rat, ~1.0 mg/mL, clone USP 3D8, purified immunoglobulin, buffered aqueous solution
04260
N-Ethylmaleimide, purum p.a., ≥99.0% (HPLC)
C6H7NO2
PLA0009
Rabbit anti-USP7 Antibody, Affinity Purified, Powered by Bethyl Laboratories, Inc.