Suppression of PPAR gamma through MKRN1-mediated ubiquitination and degradation prevents adipocyte differentiation
CELL DEATH AND DIFFERENTIATION
Authors: Kim, J-H; Park, K. W.; Lee, E-W; Jang, W-S; Seo, J.; Shin, S.; Hwang, K-A; Song, J.
Abstract
The central regulator of adipogenesis, PPAR gamma, is a nuclear receptor that is linked to obesity and metabolic diseases. Here we report that MKRN1 is an E3 ligase of PPAR gamma that induces its ubiquitination, followed by proteasome-dependent degradation. Furthermore, we identified two lysine sites at 184 and 185 that appear to be targeted for ubiquitination by MKRN1. Stable overexpression of MKRN1 reduced PPAR gamma protein levels and suppressed adipocyte differentiation in 3T3-L1 and C3H10T1/2 cells. In contrast, MKRN1 depletion stimulated adipocyte differentiation in these cells. Finally, MKRN1 knockout MEFs showed an increased capacity for adipocyte differentiation compared with wild-type MEFs, with a concomitant increase of PPAR gamma and adipogenic markers. Together, these data indicate that MKRN1 is an elusive PPARc E3 ligase that targets PPARc for proteasomal degradation by ubiquitin-dependent pathways, and further depict MKRN1 as a novel target for diseases involving PPAR gamma.
A differential screen for genes expressed in the extraembryonic endodermal layer of pre-primitive streak stage chick embryos reveals expression of Apolipoprotein A1 in hypoblast, endoblast and endoderm
GENE EXPRESSION PATTERNS
Authors: Bertocchini, Federica; Stern, Claudio D.
Abstract
The lower layer of the pre-gastrulating chick embryo is an extra-embryonic tissue made up of two different cell Populations, the hypoblast and the endoblast. The hypoblast is characterized by the expression of inhibitory signalling molecules (e.g. Cerberus, Dickkopf1, Crescent) and others (e.g. Otx2, goosecoid, Hex, Hesx1/RPX, FGF8). However, no genes expressed in the endoblast have yet been found. We designed a differential screen to identify markers differentially expressed in these two cell populations. This only revealed one novel gene, Apolipoprotein A1 (APO A1) with restricted endodermal layer expression. Expression of APO A I begins very early throughout the lower layer (both hypoblast and endoblast). At later stages it is also expressed in the endoderm and its derivatives, the anterior intestinal portal endoderm and the growing liver bud. (C) 2008 Elsevier B.V. All rights reserved.