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@ARTICLE{Menge:281808,
      author       = {Menge, Sonja and Segura, Inmaculada and Hartmann, Max and
                      Decker, Lorena and Kiran, Selin and Danzer, Karin M and
                      Iben, Sebastian and Harbauer, Angelika B and Oeckl, Patrick
                      and Freischmidt, Axel},
      title        = {{C}omparing loss of individual fragile {X} proteins
                      suggests strong links to cellular senescence and aging.},
      journal      = {Cellular and molecular life sciences},
      volume       = {82},
      number       = {1},
      issn         = {1420-682X},
      address      = {Cham (ZG)},
      publisher    = {Springer International Publishing AG},
      reportid     = {DZNE-2025-01194},
      pages        = {358},
      year         = {2025},
      abstract     = {Members of the fragile X protein (FXP) family (FMR1, FXR1
                      and FXR2) are differentially expressed in most types of
                      cancer and major neurodegenerative diseases. While increased
                      expression of FXR1 in cancer has been linked to senescence
                      evasion and consequently tumor initiation and progression,
                      decreased expression of FXPs in neurodegeneration may
                      contribute to pathogenic protein aggregation and death of
                      vulnerable neurons. However, due the causal role in fragile
                      x syndrome, most data are available about loss of FMR1 in
                      neurons while functions of FXR1 and especially FXR2 remain
                      largely unexplored. To address this knowledge gap, and to
                      directly compare functions of the FXPs, we used proteomics
                      of CRISPR/Cas9 edited HAP1 cells carrying knockouts of the
                      individual FXPs for identification of cellular mechanisms
                      associated with these proteins. Further exploration of
                      proteomic findings suggests roles of the FXPs in ribosome
                      biogenesis, autophagy and mitochondrial health linked to
                      organismal aging, and cellular senescence. Validation of FXP
                      induced defects relevant for neurodegenerative diseases in
                      neuroblastoma cell line SH-SY5Y upon FXP knockdown revealed
                      high cell type specificity of individual FXP functions.
                      Overall, we provide a comprehensive overview and comparison
                      of cellular mechanisms related to the individual FXPs, as
                      well as starting points for further studying this protein
                      family in respective cell types of FXP associated diseases,
                      and in aging in general.},
      keywords     = {Humans / Cellular Senescence: genetics / Fragile X Mental
                      Retardation Protein: genetics / Fragile X Mental Retardation
                      Protein: metabolism / Aging: genetics / Aging: metabolism /
                      RNA-Binding Proteins: metabolism / RNA-Binding Proteins:
                      genetics / CRISPR-Cas Systems / Autophagy / Cell Line, Tumor
                      / Proteomics: methods / Mitochondria: metabolism / Fragile X
                      Syndrome: metabolism / Fragile X Syndrome: genetics /
                      Fragile X Syndrome: pathology / Neurodegenerative Diseases:
                      metabolism / Neurodegenerative Diseases: genetics /
                      Neurodegenerative Diseases: pathology / Alzheimer’s
                      disease (Other) / Amyotrophic lateral sclerosis (Other) /
                      Fragile x syndrome (Other) / Parkinson’s disease (Other) /
                      Protein aggregation (Other) / Fragile X Mental Retardation
                      Protein (NLM Chemicals) / RNA-Binding Proteins (NLM
                      Chemicals) / FMR1 protein, human (NLM Chemicals) / FXR1
                      protein, human (NLM Chemicals)},
      cin          = {AG Danzer / AG Öckl},
      ddc          = {610},
      cid          = {I:(DE-2719)5000072 / I:(DE-2719)5000073},
      pnm          = {352 - Disease Mechanisms (POF4-352) / 353 - Clinical and
                      Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41117937},
      doi          = {10.1007/s00018-025-05898-0},
      url          = {https://pub.dzne.de/record/281808},
}