The protein kinase Akt/PKB regulates both prelamin A degradation and Lmna gene expression

Jessika Bertacchini, Francesca Beretti, Vittoria Cenni, Marianna Guida, Federica Gibellini, Laura Mediani, Oriano Marin, Nadir M. Maraldi, Anto De Pol, Giovanna Lattanzi, Lucio Cocco, Sandra Marmiroli

Research output: Contribution to journalArticle

Abstract

The serine/threonine kinase Akt/PKB is a major signaling hub integrating metabolic, survival, growth, and cell cycle regulatory signals. The definition of the phospho-motif cipher driving phosphorylation by Akt led to the identification of hundreds of putative substrates, and it is therefore pivotal to identify those whose phosphorylation by Akt is of consequence to biological processes. The Lmna gene products lamin A/C and the lamin A precursor prelamin A are type V intermediate filament proteins forming a filamentous meshwork, the lamina, underneath the inner nuclear membrane, for nuclear envelope structures organization and interphase chromatin anchoring. In our previous work, we reported that A-type lamins are phosphorylated by Akt at S301 and S404 in physiological conditions and are therefore bona fide substrates of Akt. We report here that Akt phosphorylation at S404 targets the precursor prelamin A for degradation. We further demonstrate that Akt also regulates Lmna transcription. Our study unveils a previously unknown function of Akt in the control of prelamin A stability and expression. Moreover, given the large number of diseases related to prelamin A, our findings represent a further important step bridging basic A-type lamin physiology to therapeutic approaches for lamin A-linked disorders.

Original languageEnglish
Pages (from-to)2145-2155
Number of pages11
JournalFASEB Journal
Volume27
Issue number6
DOIs
Publication statusPublished - Jun 2013

Keywords

  • 14.3.3
  • Cell cycle
  • Lamina phosphorylation
  • Nuclear signaling
  • Nucleus

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

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  • Cite this

    Bertacchini, J., Beretti, F., Cenni, V., Guida, M., Gibellini, F., Mediani, L., Marin, O., Maraldi, N. M., De Pol, A., Lattanzi, G., Cocco, L., & Marmiroli, S. (2013). The protein kinase Akt/PKB regulates both prelamin A degradation and Lmna gene expression. FASEB Journal, 27(6), 2145-2155. https://doi.org/10.1096/fj.12-218214