Role of C/EBP homologous protein (CHOP-10) in the programmed activation of CCAAT/enhancer-binding protein-β during adipogenesis

被引：137

作者：

Tang, QQ ^{[1
]}

Lane, MD ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21209 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2000年 / 97卷 / 23期

关键词：

3T3-L1; preadipocyte; adipocyte; differentiation; centromere; mitotic clonal expansion;

D O I：

10.1073/pnas.220425597

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 ; 0710 ; 09 ;

摘要：

Hormone induction of growth-arrested preadipocytes triggers mitotic clonal expansion followed by expression of CCAAT/enhancer-binding protein (C/EBP)alpha and differentiation into adipocytes. The order of these events is critical because C/EBP alpha is antimitotic and its expression prematurely would block the mitotic: clonal expansion required for differentiation. C/EBP beta, a transcriptional activator of the C/EBP alpha gene, is expressed early in the differentiation program. but lacks DNA-binding activity and fails to localize to centromeres until preadipocytes traverse the G(1)-S checkpoint of mitotic clonal expansion. Evidence is presented that dominant-negative CHOP-10 expressed by growth-arrested preadipocytes transiently sequesters C/EBP beta by heterodimerization. As preadipocytes reach S phase, CHOP-10 is down-regulated, apparently releasing C/EBP beta from inhibitory constraint and allowing transactivation of the C/EBP alpha gene. In support of these findings, up-regulation of CHOP-10 with the protease inhibitor N-acetyl-Leu-Leu-norleucinal prevents activation of C/EBP beta. expression of C/EBP alpha, and adipogenesis.

引用

页码：12446 / 12450

页数：5

共 18 条

[1]

BERNLOHR DA, 1985, J BIOL CHEM, V260, P5563

[2] Phosphorylation of rat serine 105 or mouse threonine 217 in C/EBPβ is required for hepatocyte proliferation induced by TGFα [J].

Buck, M ;

Poli, V ;

van der Geer, P ;

Chojkier, M ;

Hunter, T .

MOLECULAR CELL, 1999, 4 (06) :1087-1092

[3] REGULATED EXPRESSION OF 3 C/EBP ISOFORMS DURING ADIPOSE CONVERSION OF 3T3-L1 CELLS [J].

CAO, ZD ;

UMEK, RM ;

MCKNIGHT, SL .

GENES & DEVELOPMENT, 1991, 5 (09) :1538-1552

[4] SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION [J].

CHOMCZYNSKI, P ;

SACCHI, N .

ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) :156-159

[5] CCAAT ENHANCER BINDING-PROTEIN GENE PROMOTER - BINDING OF NUCLEAR FACTORS DURING DIFFERENTIATION OF 3T3-L1 PREADIPOCYTES [J].

CHRISTY, RJ ;

KAESTNER, KH ;

GEIMAN, DE ;

LANE, MD .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (06) :2593-2597

[6] CCAAT enhancer-binding protein β is required for normal hepatocyte proliferation in mice after partial hepatectomy [J].

Greenbaum, LE ;

Li, W ;

Cressman, DE ;

Peng, Y ;

Ciliberto, G ;

Poli, V ;

Taub, R .

JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (05) :996-1007

[7] A 30-KDA ALTERNATIVE TRANSLATION PRODUCT OF THE CCAAT ENHANCER-BINDING PROTEIN-ALPHA MESSAGE - TRANSCRIPTIONAL ACTIVATOR LACKING ANTIMITOTIC ACTIVITY [J].

LIN, FT ;

MACDOUGALD, OA ;

DIEHL, AM ;

LANE, MD .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (20) :9606-9610

[8] ANTISENSE CCAAT ENHANCER-BINDING PROTEIN RNA SUPPRESSES COORDINATE GENE-EXPRESSION AND TRIGLYCERIDE ACCUMULATION DURING DIFFERENTIATION OF 3T3-L1 PREADIPOCYTES [J].

LIN, FT ;

LANE, MD .

GENES & DEVELOPMENT, 1992, 6 (04) :533-544

[9] TRANSCRIPTIONAL REGULATION OF GENE-EXPRESSION DURING ADIPOCYTE DIFFERENTIATION [J].

MACDOUGALD, OA ;

LANE, MD .

ANNUAL REVIEW OF BIOCHEMISTRY, 1995, 64 :345-373

[10] Role of calpain in adipocyte differentiation [J].

Patel, YM ;

Lane, MD .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (04) :1279-1284

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