Identification of a functional nuclear export sequence in diacylglycerol kinase-ζ

Camilla Evangelisti, Gian Carlo Gaboardi, Anna Maria Billi, Andrea Ognibene, Kaoru Goto, Pier Luigi Tazzari, James A. McCubrey, Alberto M. Martelli

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Diacylglycerol kinases (DGKs) are key regulators of diacylglycerol- dependent signaling pathways. Among the 10 DGK isoforms, DGK-ζ is the only nuclear form that contains a nuclear localization signal. Here, by site-directed mutagenesis, we showed that DGK-ζ also displays a functional independent nuclear export signal (NES) sequence between the amino acid residues 362-370. Indeed, the NES mutant forms of DGK-ζ accumulated in the nucleus to a much greater extent than wild type DGK-ζ. Moreover, treatment with leptomycin B, an inhibitor of leucine-rich type NES, resulted in accumulation of both endogenous and ectopically expressed DGK-ζ in the nucleus, demonstrating that nuclear export of DGK-ζ is chromosome regional maintenance protein 1 (CRM1)-dependent. Previously, we reported that nuclear DGK-ζ is a negative regulator of cell cycle progression in C2C12 mouse myoblasts. In this paper, we documented that enhancement of DGK-ζ nuclear localization by NES sequence mutation, increases G0/G1 block in C2C12 cells. Overall, our data demonstrate that DGK-ζ export from nucleus to cytoplasm is regulated by a leucine-rich NES through the exportin CRM1 and suggest that the nuclear localization of DGK-ζ could finely tune its function as a regulator of G1/S cell cycle transition.

Original languageEnglish
Pages (from-to)384-388
Number of pages5
JournalCell Cycle
Volume9
Issue number2
DOIs
Publication statusPublished - Jan 15 2010

Fingerprint

Diacylglycerol Kinase
Cell Nucleus Active Transport
Nuclear Export Signals
Protein Sorting Signals
Leucine
Cell Cycle
Chromosomes
Maintenance
Karyopherins
Nuclear Localization Signals
Myoblasts
Diglycerides
Site-Directed Mutagenesis

Keywords

  • Cell cycle
  • CRM1
  • Diacylglycerol kinase
  • NES
  • Nucleus

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Evangelisti, C., Gaboardi, G. C., Billi, A. M., Ognibene, A., Goto, K., Tazzari, P. L., ... Martelli, A. M. (2010). Identification of a functional nuclear export sequence in diacylglycerol kinase-ζ. Cell Cycle, 9(2), 384-388. https://doi.org/10.4161/cc.9.2.10469

Identification of a functional nuclear export sequence in diacylglycerol kinase-ζ. / Evangelisti, Camilla; Gaboardi, Gian Carlo; Billi, Anna Maria; Ognibene, Andrea; Goto, Kaoru; Tazzari, Pier Luigi; McCubrey, James A.; Martelli, Alberto M.

In: Cell Cycle, Vol. 9, No. 2, 15.01.2010, p. 384-388.

Research output: Contribution to journalArticle

Evangelisti, C, Gaboardi, GC, Billi, AM, Ognibene, A, Goto, K, Tazzari, PL, McCubrey, JA & Martelli, AM 2010, 'Identification of a functional nuclear export sequence in diacylglycerol kinase-ζ', Cell Cycle, vol. 9, no. 2, pp. 384-388. https://doi.org/10.4161/cc.9.2.10469
Evangelisti C, Gaboardi GC, Billi AM, Ognibene A, Goto K, Tazzari PL et al. Identification of a functional nuclear export sequence in diacylglycerol kinase-ζ. Cell Cycle. 2010 Jan 15;9(2):384-388. https://doi.org/10.4161/cc.9.2.10469
Evangelisti, Camilla ; Gaboardi, Gian Carlo ; Billi, Anna Maria ; Ognibene, Andrea ; Goto, Kaoru ; Tazzari, Pier Luigi ; McCubrey, James A. ; Martelli, Alberto M. / Identification of a functional nuclear export sequence in diacylglycerol kinase-ζ. In: Cell Cycle. 2010 ; Vol. 9, No. 2. pp. 384-388.
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