Enhanced expression of the nuclear envelope LAP2 transcriptional repressors in normal and malignant activated lymphocytes.
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 LAP2beta 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 LAP2beta, while slowly proliferating malignant cells of chronic malignant hematological diseases do not. Taking together the elevated expression of LAP2beta 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.
Somech
Raz
R
Sheba Cancer Research Center, Institute of Hematology, Chaim Sheba Medical Center, Tel-Hashomer, Israel. rsomech@hotmail.com
Gal-Yam
Einav Nili
EN
Shaklai
Sigal
S
Geller
Orit
O
Amariglio
Ninette
N
Rechavi
Gideon
G
Simon
Amos J
AJ
D004268:DNA-Binding Proteins / Q000378:metabolism*; D019337:Hematologic Neoplasms / Q000378:metabolism*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008232:Lymphoproliferative Disorders / Q000097:blood / Q000503:physiopathology*; D008565:Membrane Proteins / Q000378:metabolism*; D009685:Nuclear Envelope / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology; D015854:Up-Regulation; D000099186:Histone Deacetylase 3
D004268:DNA-Binding Proteins; D006655:Histone Deacetylases; D008565:Membrane Proteins; D000099186:Histone Deacetylase 3; C093413:lamina-associated polypeptide 2