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Nuclear envelope protein lamin B receptor protects the genome from chromosomal instability and tumorigenesis.
Patil, Shalaka; Deshpande, Shruti; Sengupta, Kundan.
Affiliation
  • Patil S; Chromosome Biology Lab (CBL), Indian Institute of Science Education and Research (IISER), Pune 411008, India.
  • Deshpande S; Chromosome Biology Lab (CBL), Indian Institute of Science Education and Research (IISER), Pune 411008, India.
  • Sengupta K; Chromosome Biology Lab (CBL), Indian Institute of Science Education and Research (IISER), Pune 411008, India.
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.
Subject(s)

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:

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: