Ask about this productRelated genes to: LEMD2 antibody
- Gene:
- LEMD2 NIH gene
- Name:
- LEM domain containing 2
- Previous symbol:
- -
- Synonyms:
- dJ482C21.1, NET25, LEM2
- Chromosome:
- 6p21.31
- Locus Type:
- gene with protein product
- Date approved:
- 2003-05-29
- Date modifiied:
- 2019-02-22
Related products to: LEMD2 antibody
Related articles to: LEMD2 antibody
- Nuclear envelope dysfunction is increasingly recognized as a driver of cancer-associated alterations in chromatin organization, genome stability, and mechanotransduction. Among inner nuclear membrane components are the LEM-domain (LEM-D) proteins LAP2/TMPO, emerin (EMD), LEMD1, LEMD2, MAN1/LEMD3, ANKLE1, and ANKLE2. Accumulating evidence links dysregulation of these proteins to hallmark cancer processes, including cell-cycle control, epithelial-mesenchymal transition, genome instability, and therapeutic resistance. This review synthesizes recent mechanistic and translational findings on LEM-D proteins in cancer, highlighting isoform-specific functions, context-dependent oncogenic versus tumor-suppressive roles, and convergence on key pathways such as Wnt/β-catenin, PI3K/AKT, MAPK, and TGF-β signaling. Concrete evidence for prognostic value varies across the LEM-D proteins. While much of the current evidence derives from transcript-level and preclinical studies, emerging data suggest that LEM-D proteins contribute to nuclear stress adaptation and may represent context-dependent therapeutic vulnerabilities. We discuss their prognostic and predictive potential, critically evaluate limitations in current datasets, and present a unifying framework linking LEM-D dysfunction to genome instability, altered signalling, and therapy resistance. Thus, despite growing evidence of therapeutic potential, these proteins are better positioned as biomarkers to guide current therapies. - Source: PubMed
Publication date: 2026/04/22
Jobe AmieMirza SameerVijayan Ranjit - In open mitosis, a single nuclear envelope (NE) forms around segregated chromosomes despite an excess of membrane-chromatin tethers. Here, we identify a hierarchical relationship between the BAF binding membrane tethers LEM-2 and Emerin, in which LEM-2 preferentially accumulates at BAF binding sites during postmitotic NE assembly and limits Emerin accumulation in embryos. When LEM-2 is absent, Emerin occupies these sites and compensates for LEM-2 loss; however, NE formation becomes sensitized to ER membrane abundance - excessive phospholipid production through loss of CTDNEP1/CNEP-1 causes membrane invasions in interchromosomal regions and, across multiple systems, formation of lobulated, unstable nuclei with abnormal Emerin accumulations. We find that human CTDNEP1 regulates the NE-associated enzyme CCTα to maintain phosphatidylcholine (PC) homeostasis through preventing delayed PC breakdown. Restoring PC levels rescues Emerin assembly and nuclear morphology defects resulting from the combined loss of CTDNEP1 and LEMD2. Together, these findings link membrane-chromatin tethering to ER lipid content and reveal preferential tethering as a determinant of NE assembly fidelity, with broad relevance to disease-related nuclear defects. - Source: PubMed
Publication date: 2026/03/02
Barger Sarah RSepúlveda SofiaYang HanGoudge MarcLee ShokenRidgway Neale DBahmanyar Shirin - Haploinsufficiency of Lap2 alpha (LAP2a), a nuclear partner of Lamins A/C, has been associated with cardiac disease in rare cases, but LAP2a function remains largely unknown. To investigate the functional role of LAP2a in cardiomyocytes, we generated clones of embryonic myocardium-derived H9C2 cells in which LAP2a expression was specifically reduced through gene editing of the LAP2a gene by CRISPR-Cas9. Downregulation (+/-) and absence (-/-) of LAP2a expression led to a decreased proliferation capacity of cardiomyocytes . Upon differentiation, the expression of myocardial markers (alpha cardiac Actin 1/, cardiac Troponin T2/, Myosin-2/ and Myosin-7/) was higher in LAP2a -/- cells compared to LAP2a +/- or LAP2a +/+ cells, with consistently higher expression of their upstream regulator in LAP2a-devoid cells. These results suggest that LAP2a promotes cardiomyocyte proliferation and negatively modulates cardiomyocyte differentiation, through mechanisms including regulation. Accordingly, normal protein expression of LAP2a was downregulated upon cardiomyocyte differentiation, contrary to LAP2b and a LAP2b-related shorter isoform. The latter tended to increase upon differentiation in all cells, most significantly in the LAP2a -/- clone. In postnatal mouse hearts, LAP2a levels were higher in the right than in the left ventricle, and lowest in the septum. The LAP2a:LAP2b ratio was much lower in murine hearts than in H9C2 cells, and decreased significantly upon ageing, specifically in the left ventricle. Finally, our data show that expression of the nuclear envelope proteins LEMD2 and Lamin A might be influenced by LAP2a upon cardiac differentiation. Our results show that LAP2 expression is finely regulated upon cardiac differentiation and is dependent on age and heart compartment They contribute to clarifying the potential impact of genetic LAP2a defects and their connection with heart disease, possibly including reduced cardiomyoblast proliferation, increased cardiomyocyte differentiation and altered nuclear envelope remodelling. - Source: PubMed
Publication date: 2026/01/21
Vadrot NathalieMoulin MarylineFerreiro AnaRichard PascaleBuendia Brigitte - Proteomics-guided exome re-analysis identifies bi-allelic variants in the nuclear envelope LEMD2 gene, expanding its phenotypic spectrum. Created in BioRender. Pauper, M. (2026) https://BioRender.com/xamvo92. - Source: PubMed
Publication date: 2026/03/03
Pauper MarcKölbel HeikeKarakesisoglou IakowosSchänzer AnneBöhm JohannThompson RachelKohlschmidt NicolaiRingel BerndBonne GisèleNeuhoff KatjaGangfuß AndreaKilicarslan Ozge AkselAgullo Sergi BeltranHentschel AndreasSchara-Schmidt UlrikeLochmüller HannsPolavarapu KiranRoos Andreas - The epigenome and nuclear architectural mechanisms that regulate neuronal activity-induced transcriptional responses in cortical neurons remain incompletely understood. Previously, we have shown that the chromatin organizer SATB2 and the inner nuclear membrane protein LEMD2 form a chromatin tether at the nuclear lamina, and that activity-induced transcription is impaired in both and loss-of-function models. Interaction of SATB2 and LEMD2 with subunits of the ESCRT-III complex indicates that the ESCRT-III complex could serve as an activity-dependent, dynamic component of this tether. Here, we study the activity-dependent subcellular localization and function of the ESCRT-III components CHMP7 and CHMP4B in primary cortical neurons. We find that increased neuronal activity correlates with the accumulation of co-localized CHMP7 and CHMP4B foci at the nuclear envelope. shRNA-mediated knockdown causes a reduction in the expression of activity-regulated genes and genes with highly specialized functions in synaptic organization and trans-synaptic signaling. Furthermore, the observed similarity in the global transcriptome responses in , , and loss-of-function models points toward a previously unrecognized role of the SATB2-LEMD2-CHMP7 tether in linking chromatin architecture and nuclear envelope plasticity to activity-dependent gene regulation. - Source: PubMed
Publication date: 2026/02/10
Chietera PaolaBerger HeidrunWahl NicoAli MujahidApostolova Galina