Enhanced expression of the nuclear envelope LAP2 transcriptional repressors in normal and malignant activated lymphocytes

Raz Somech, Einav Nili Gal-Yam, Sigal Shaklai, Orit Geller, Ninette Amariglio, Gideon Rechavi, Amos J. Simon

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Extensive research in recent years has broadened the functions of nuclear envelope proteins beyond simply stabilizing the nucleus architecture. Particularly, integral nuclear membrane proteins, such as the alternative spliced isoforms of lamina-associated polypeptide 2 (LAP2), have been shown to be important for the initiation of replication and repression of transcription. The latter is regulated by epigenetic changes, induced by the binding of LAP2β to histone deacetylase-3 (HDAC3), resulting in histone H4 deacetylation. Involvement of nuclear envelope proteins in pathological proliferative conditions, mainly those involving abnormal recruitment and activation of HDACs, is still unknown. In this paper, we show that various nuclear envelope proteins are highly expressed in normal and malignant activated lymphocytes. Specifically, rapidly replicating cells of various hematological malignancies highly express LAP2β, while slowly proliferating malignant cells of chronic malignant hematological diseases do not. Taking together the elevated expression of LAP2β in highly proliferative malignant cells with its known ability to modify histones through binding with HDAC3 raises the possibility of its role in hematological malignancies involving aberrant activity of HDAC3. Based on our presented results, we believe that the LAP2-HDAC regulatory pathway should be studied as a new target for rational therapy.

Original languageEnglish (US)
Pages (from-to)393-401
Number of pages9
JournalAnnals of hematology
Volume86
Issue number6
DOIs
StatePublished - Jun 1 2007

Fingerprint

Nuclear Lamina
Nuclear Envelope
Nuclear Proteins
Lymphocytes
Hematologic Neoplasms
Histones
Hematologic Diseases
Epigenomics
Protein Isoforms
Membrane Proteins
lamina-associated polypeptide 2
Research
histone deacetylase 3

Keywords

  • Epigenetic histone modifications
  • HDAC3
  • LAP2
  • Nuclear envelope
  • Transcriptional repression

ASJC Scopus subject areas

  • Hematology

Cite this

Enhanced expression of the nuclear envelope LAP2 transcriptional repressors in normal and malignant activated lymphocytes. / Somech, Raz; Nili Gal-Yam, Einav; Shaklai, Sigal; Geller, Orit; Amariglio, Ninette; Rechavi, Gideon; Simon, Amos J.

In: Annals of hematology, Vol. 86, No. 6, 01.06.2007, p. 393-401.

Research output: Contribution to journalArticle

Somech, Raz ; Nili Gal-Yam, Einav ; Shaklai, Sigal ; Geller, Orit ; Amariglio, Ninette ; Rechavi, Gideon ; Simon, Amos J. / Enhanced expression of the nuclear envelope LAP2 transcriptional repressors in normal and malignant activated lymphocytes. In: Annals of hematology. 2007 ; Vol. 86, No. 6. pp. 393-401.
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