Nuclear envelope protein lamin B receptor protects the genome from chromosomal instability and tumorigenesis.
Hum Mol Genet
; 32(5): 745-763, 2023 02 19.
Article
in En
| MEDLINE
| ID: mdl-36124691
ABSTRACT
Lamin B Receptor (LBR) is an inner nuclear membrane protein that assembles the nuclear envelope post mitosis. Here we show that LBR depletion induces mitotic defects accompanied by recurrent chromosomal losses. In addition, LBR knockdown results in nuclear aberrations such as nuclear blebs and micronuclei, with chromosomes showing higher frequency of losses, being enriched within the micronucleus. Furthermore, doxycycline-induced conditional depletion of LBR significantly increased tumor volumes that form within the subcutaneous xenografts of mice. Of note, the tumor-derived primary cells recapitulated chromosomal losses and gains, revealing a novel role for LBR as a tumor suppressor. Co-immunoprecipitation of LBR uncovered an association of LBR with telomere-associated factors. Interestingly, qPCR array-based gene expression profiling showed a significant upregulation of telomere repeat-binding factor 1 (TRF1) upon LBR depletion. Remarkably, TRF1 knockdown in the background of LBR depletion maintains chromosomal stability, unraveling a novel mechanism involving LBR and TRF in the maintenance of chromosomal stability in colorectal cancer cells.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptors, Cytoplasmic and Nuclear
/
Nuclear Envelope
Limits:
Animals
/
Humans
Language:
En
Journal:
Hum Mol Genet
Journal subject:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Year:
2023
Document type:
Article
Affiliation country: