Interaction between HMGA1 and retinoblastoma protein is required for adipocyte differentiation

Francesco Esposito, Giovanna Maria Pierantoni, Sabrina Battista, Rosa Marina Mellillo, Stefania Scala, Paolo Chieffi, Monica Fedele, Alfredo Fusco

Research output: Contribution to journalArticlepeer-review

Abstract

It is generally accepted that the regulation of adipogenesis prevents obesity. However, the mechanisms controlling adipogenesis have not been completely defined. We have previously demonstrated that HMGA1 proteins play a critical role in adipogenesis. In fact, suppression of HMGA1 protein synthesis by antisense technology dramatically increased growth rate and impaired adipocyte differentiation in 3T3-L1 cells. Furthermore, we showed that HMGA1 strongly potentiates the capacity of the CCAAT/enhancer-binding protein β (C/EBPβ) transcriptional factor to transactivate the leptin promoter, an adipocytic-specific promoter. In this study we demonstrate that HMGA1 physically interacts with retinoblastoma protein (RB), which is also required in adipocyte differentiation. Moreover, we show that RB, C/EBPβ, and HMGA1 proteins all cooperate in controlling both Id1 and leptin gene transcriptions, which are down- and up-regulated during adipocyte differentiation, respectively. We also demonstrate that HMGA1/RB interaction regulates CDC25A and CDC6 promoter activities, which are induced by E2F-1 protein during early adipocyte differentiation, by displacingHDAC1from the RB-E2F1 complex. Furthermore, by using Hmga1-/- embryonic stem cells, which failed to undergo adipocyte differentiation, we show the crucial role of HMGA1 proteins in adipocyte differentiation due to its pivotal involvement in the formation of the RB-C/EBPβ complex. Altogether these data demonstrate a key role of the interaction between HMGA1 and RB in adipocyte differentiation.

Original languageEnglish
Pages (from-to)25993-26004
Number of pages12
JournalJournal of Biological Chemistry
Volume284
Issue number38
DOIs
Publication statusPublished - Sep 18 2009

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

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