𝔖 Bobbio Scriptorium
✦   LIBER   ✦

Helenalin-mediated post-transcriptional regulation of p21(Cip1) inhibits 3T3-L1 preadipocyte proliferation

✍ Scribed by Karishma M. Fernandes; Corinth A. Auld; Robin G. Hopkins; Ron F. Morrison

Publisher
John Wiley and Sons
Year
2008
Tongue
English
Weight
217 KB
Volume
105
Category
Article
ISSN
0730-2312

No coin nor oath required. For personal study only.

✦ Synopsis

Abstract

We have previously shown that post‐transcriptional mechanisms involving the 26S proteasome regulate the cyclin‐dependent kinase inhibitors (CKIs), p21(Cip1) and p27(Kip1) during preadipocyte proliferation. Earlier studies further demonstrated that the anti‐inflammatory, anti‐carcinogenic phytochemical, helenalin is a potent inhibitor of periodic Skp2 accumulation, an F‐box protein mediating SCF E3 ligase ubiquitylation and degradation of both CKIs during S phase progression. Data presented here demonstrate that helenalin dose‐dependently induced G1 arrest of synchronously replicating 3T3‐L1 preadipocytes. This effect occurred in the absence of discernable indices of cell toxicity or apoptosis under the conditions used in this study. Our results demonstrate that helenalin markedly increased p21 protein accumulation in both density‐arrested and proliferating preadipocytes in a dose‐dependent manner. This increase in p21 protein abundance occurred without change in mRNA transcript demonstrating that post‐transcriptional mechanisms were involved. This notion was further supported by the modest accumulation of polyubiquitylated p21 following treatment with helenalin suggesting that suppression of targeted p21 proteolysis by the 26S proteasome contributed to helenalin‐mediated p21 accumulation. The increase in p21 protein was compartmentalized to the nucleus where p21 is known to inhibit cell cycle progression. Finally, helenalin increased protein–protein interactions between p21 and cyclin‐dependent kinase 2 (Cdk2) which may account in part for the anti‐proliferative effect in 3T3‐L1 preadipocytes. J. Cell. Biochem. 105: 913–921, 2008. © 2008 Wiley‐Liss, Inc.

📜 SIMILAR VOLUMES

Characterization of the transcriptional
Characterization of the transcriptional regulation of the regulator of G protein signaling 2 (RGS2) gene during 3T3-L1 preadipocyte differentiation
✍ Ya-Shan Cheng; Tzong-Shyuan Lee; Hui-Chi Hsu; Yu Ru Kou; Yuh-Lin Wu 📂 Article 📅 2008 🏛 John Wiley and Sons 🌐 English ⚖ 267 KB

## Abstract Adipocyte differentiation is a complex process involving several signaling pathways. Molecular mechanisms regulating the very early stage of adipocyte differentiation is not fully appreciated yet. Several inducible genes at the early stage of preadipocyte differentiation have been ident

Up-regulation of p21CIP1 expression medi
Up-regulation of p21CIP1 expression mediated by ERK-dependent and -independent pathways contributes to hepatocyte growth factor-induced inhibition of HepG2 hepatoma cell proliferation
✍ Erika Shirako; Naoki Hirayama; Yu-ichi Tsukada; Toshiaki Tanaka; Naomi Kitamura 📂 Article 📅 2008 🏛 John Wiley and Sons 🌐 English ⚖ 358 KB 👁 2 views

## Abstract Strong activation of the ERK signal is required for hepatocyte growth factor (HGF) to inhibit proliferation of the human hepatocellular carcinoma cell line HepG2. However, it is still to be elucidated whether the activation alone is sufficient to induce the inhibitory effect. In this st

Prostaglandin F2α induces the normoxic a
Prostaglandin F2α induces the normoxic activation of the hypoxia-inducible factor-1 transcription factor in differentiating 3T3-L1 preadipocytes: Potential role in the regulation of adipogenesis
✍ Li Liu; Neil A. Clipstone 📂 Article 📅 2008 🏛 John Wiley and Sons 🌐 English ⚖ 228 KB

## Abstract Prostaglandin F2α (PGF2α) is a potent paracrine inhibitor of adipocyte differentiation. Here we show that treatment of differentiating 3T3‐L1 preadipocytes with PGF2α induces the expression of DEC1, a transcriptional repressor that has previously been implicated in the inhibition of adi