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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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
Pages (from-to)393-401
Number of pages9
JournalAnnals of Hematology
Volume86
Issue number6
DOIs
StatePublished - Jun 2007

Funding

FundersFunder number
Israel Science Fund804

    Keywords

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

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