PERK-dependent regulation of lipogenesis during mouse mammary gland development and adipocyte differentiation

被引：234

作者：

Bobrovnikova-Marjon, Ekaterina ^{[1
,2
,3
]}

Hatzivassiliou, Georgia ^{[1
,2
]}

Grigoriadou, Christina ^{[1
,2
,3
]}

Romero, Margarita ^{[1
,2
]}

Cavener, Douglas R. ^{[4
]}

Thompson, Craig B. ^{[1
,2
,3
]}

Diehl, J. Alan ^{[1
,2
,3
]}

机构：

[1] Univ Penn, Leonard & Madlyn Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA

[2] Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA

[3] Univ Penn, Dept Canc Biol, Philadelphia, PA 19104 USA

[4] Penn State Univ, Dept Biol, University Pk, PA 16802 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2008年 / 105卷 / 42期

基金：

美国国家卫生研究院;

关键词：

lipid metabolism; SREBP1; FAS; ACL; fatty acids;

D O I：

10.1073/pnas.0808517105

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 [理学]; 0710 [生物学]; 09 [农学];

摘要：

The role of the endoplasmic reticulum stress-regulated kinase, PERK, in mammary gland function was assessed through generation of a targeted deletion in mammary epithelium. Characterization revealed that PERK is required for functional maturation of milk-secreting mammary epithelial cells. PERK-dependent signaling contributes to lipogenic differentiation in mammary epithelium, and perk deletion inhibits the sustained expression of lipogenic enzymes FAS, ACL, and SCD1. As a result, mammary tissue has reduced lipid content and the milk produced has altered lipid composition, resulting in attenuated pup growth. Consistent with PERK-dependent regulation of the lipogenic pathway, loss of PERK inhibits expression of FAS, ACL, and SCD1 in immortalized murine embryonic fibroblasts when cultured under conditions favoring adipocyte differentiation. These findings implicate PERK as a physiologically relevant regulator of the lipogenic pathway.

引用

页码：16314 / 16319

页数：6

共 44 条

[1]

Key stages in mammary gland development - Secretory activation in the mammary gland: it's not just about milk protein synthesis! [J].

Anderson, Steven M. ;

Rudolph, Michael C. ;

McManaman, James L. ;

Neville, Margaret C. .

BREAST CANCER RESEARCH, 2007, 9 (01)

[2]

ATP citrate lyase is an important component of cell growth and transformation [J].

Bauer, DE ;

Hatzivassiliou, G ;

Zhao, FP ;

Andreadis, C ;

Thompson, CB .

ONCOGENE, 2005, 24 (41) :6314-6322

[3]

BLIGH EG, 1959, CAN J BIOCHEM PHYS, V37, P911

[4]

PERK mediates cell-cycle exit during the mammalian unfolded protein response [J].

Brewer, JW ;

Diehl, JA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (23) :12625-12630

[5]

Endoplasmic reticulum stress causes the activation of sterol regulatory element binding protein-2 [J].

Colgan, Stephen M. ;

Tang, Darnu ;

Werstuck, Geoff H. ;

Austin, Richard C. .

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2007, 39 (10) :1843-1851

[6]

INHIBITION OF GLYCOGEN-SYNTHASE KINASE-3 BY INSULIN-MEDIATED BY PROTEIN-KINASE-B [J].

CROSS, DAE ;

ALESSI, DR ;

COHEN, P ;

ANDJELKOVICH, M ;

HEMMINGS, BA .

NATURE, 1995, 378 (6559) :785-789

[7]

Transcriptional regulation of metabolism [J].

Desvergne, B ;

Michalik, L ;

Wahli, W .

PHYSIOLOGICAL REVIEWS, 2006, 86 (02) :465-514

[8]

Involvement of Akt in ER-to-Golgi transport of SCAP/SREBP: A link between a key cell proliferative pathway and membrane synthesis [J].

Du, Ximing ;

Kristiana, Ika ;

Wong, Jenny ;

Brown, Andrew J. .

MOLECULAR BIOLOGY OF THE CELL, 2006, 17 (06) :2735-2745

[9]

Regulation of sterol synthesis in eukaryotes [J].

Espenshade, Peter J. ;

Hughes, Adam L. .

ANNUAL REVIEW OF GENETICS, 2007, 41 :401-427

[10]

FOWLER SD, 1987, J LIPID RES, V28, P1225

← 1 2 3 4 5 →