Nuclear membrane protein LAP2beta mediates transcriptional repression alone and together with its binding partner GCL (germ-cell-less)

E Nili; G S Cojocaru; Y Kalma; D Ginsberg; N G Copeland; D J Gilbert; N A Jenkins; R Berger; S Shaklai; N Amariglio; F Brok-Simoni; A J Simon; G Rechavi

doi:10.1242/jcs.114.18.3297

Nuclear membrane protein LAP2beta mediates transcriptional repression alone and together with its binding partner GCL (germ-cell-less)

J Cell Sci. 2001 Sep;114(Pt 18):3297-307. doi: 10.1242/jcs.114.18.3297.

Authors

E Nili¹, G S Cojocaru, Y Kalma, D Ginsberg, N G Copeland, D J Gilbert, N A Jenkins, R Berger, S Shaklai, N Amariglio, F Brok-Simoni, A J Simon, G Rechavi

Affiliation

¹ Pediatric Hemato-Oncology Department, Division of Hematology, Chaim Sheba Medical Center, Tel-Hashomer and the Sackler School of Medicine, Tel-Aviv University, Israel.

PMID: 11591818
DOI: 10.1242/jcs.114.18.3297

Abstract

LAP2beta is an integral membrane protein of the nuclear envelope involved in chromatin and nuclear architecture. Using the yeast two-hybrid system, we have cloned a novel LAP2beta-binding protein, mGCL, which contains a BTB/POZ domain and is the mouse homologue of the Drosophila germ-cell-less (GCL) protein. In Drosophila embryos, GCL was shown to be essential for germ cell formation and was localized to the nuclear envelope. Here, we show that, in mammalian cells, GCL is co-localized with LAP2beta to the nuclear envelope. Nuclear fractionation studies reveal that mGCL acts as a nuclear matrix component and not as an integral protein of the nuclear envelope. Recently, mGCL was found to interact with the DP3alpha component of the E2F transcription factor. This interaction reduced the transcriptional activity of the E2F-DP heterodimer, probably by anchoring the complex to the nuclear envelope. We demonstrate here that LAP2beta is also capable of reducing the transcriptional activity of the E2F-DP complex and that it is more potent than mGCL in doing so. Co-expression of both LAP2beta and mGCL with the E2F-DP complex resulted in a reduced transcriptional activity equal to that exerted by the pRb protein.

Publication types

Research Support, U.S. Gov't, P.H.S.

MeSH terms

Amino Acid Sequence
Animals
Carcinoma, Non-Small-Cell Lung / metabolism
Carrier Proteins / physiology
Cell Cycle Proteins*
Chromosomes / chemistry
DNA-Binding Proteins / chemistry
DNA-Binding Proteins / metabolism*
Drosophila
Drosophila Proteins*
E2F Transcription Factors
Humans
Insulinoma / metabolism
Intercellular Signaling Peptides and Proteins
Lung Neoplasms
Macromolecular Substances
Membrane Proteins / chemistry
Membrane Proteins / metabolism*
Mice
Molecular Sequence Data
Nuclear Envelope / chemistry
Nuclear Envelope / metabolism*
Nuclear Proteins / genetics
Nuclear Proteins / isolation & purification
Nuclear Proteins / metabolism*
Pancreas / cytology
Pancreas / metabolism
Protein Transport / physiology
Saccharomyces cerevisiae
Sequence Homology
Transcription Factors / metabolism*
Transcription, Genetic / physiology
Tumor Cells, Cultured / metabolism

Substances

Carrier Proteins
Cell Cycle Proteins
DNA-Binding Proteins
DP-interacting protein, mouse
Drosophila Proteins
E2F Transcription Factors
Gcl protein, mouse
Intercellular Signaling Peptides and Proteins
Macromolecular Substances
Membrane Proteins
Nuclear Proteins
Transcription Factors
gcl protein, Drosophila
lamina-associated polypeptide 2