The implications of physiological biomolecular condensates in amyotrophic lateral sclerosis

Fakim, Hana; Velde, Christine Vande

doi:10.1016/j.semcdb.2023.05.006

Cited by 9 publications

(2 citation statements)

References 135 publications

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“…FUS and TDP-43 are RNA binding proteins that contribute to CB formation [ 5 ]. We showed here that both proteins contribute to CB organization also in prostate cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Platinum-based drugs induce phenotypic alterations in nucleoli and Cajal bodies in prostate cancer cells

Batnasan,

Kärkkäinen,

Koivukoski

et al. 2024

Cancer Cell Int

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Purpose Platinum-based drugs are cytotoxic drugs commonly used in cancer treatment. They cause DNA damage, effects of which on chromatin and cellular responses are relatively well described. Yet, the nuclear stress responses related to RNA processing are incompletely known and may be relevant for the heterogeneity with which cancer cells respond to these drugs. Here, we determine the type and extent of nuclear stress responses of prostate cancer cells to clinically relevant platinum drugs. Methods We study nucleolar and Cajal body (CB) responses to cisplatin, carboplatin, and oxaliplatin with immunofluorescence-based methods in prostate cancer cells. We utilize organelle-specific markers NPM, Fibrillarin, Coilin, and SMN1, and study CB-regulatory proteins FUS and TDP-43 using siRNA-mediated downregulation. Results Different types of prostate cancer cells have different sensitivities to platinum drugs. With equally cytotoxic doses, cisplatin, and oxaliplatin induce prominent nucleolar and CB stress responses while the nuclear stress phenotypes to carboplatin are milder. We find that Coilin is a stress-specific marker for platinum drug response heterogeneity. We also find that CB-associated, stress-responsive RNA binding proteins FUS and TDP-43 control Coilin and CB biology in prostate cancer cells and, further, that TDP-43 is associated with stress-responsive CBs in prostate cancer cells. Conclusion Our findings provide insight into the heterologous responses of prostate cancer cells to different platinum drug treatments and indicate Coilin and TDP-43 as stress mediators in the varied outcomes. These results help understand cancer drug responses at a cellular level and have implications in tackling heterogeneity in cancer treatment outcomes.

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“…FUS and TDP-43 are RNA binding proteins that contribute to CB formation [ 5 ]. We showed here that both proteins contribute to CB organization also in prostate cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Platinum-based drugs induce phenotypic alterations in nucleoli and Cajal bodies in prostate cancer cells

Batnasan,

Kärkkäinen,

Koivukoski

et al. 2024

Cancer Cell Int

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show abstract

“…Cellular condensate formation is associated with many biological processes including transcription, translation, signal transduction, and protein folding. Recently, interest in condensates has increased because of their potential role in the pathogenesis of ALS, FTD, Huntington’s disease and other neurodegenerative conditions 21 – 24 . In particular, disruption of normal condensate formation or maintenance may provide a mechanistic link to the development of these diseases 20 , 21 .…”

Section: Introductionmentioning

confidence: 99%

Pathogenic mutations in UBQLN2 exhibit diverse aggregation propensity and neurotoxicity

Safren,

Dao,

Mohan

et al. 2024

Sci Rep

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The ubiquitin-adaptor protein UBQLN2 promotes degradation of several aggregate-prone proteins implicated in neurodegenerative diseases. Missense UBQLN2 mutations also cause X-linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Previously we demonstrated that the liquid-like properties of UBQLN2 molecular assemblies are altered by a specific pathogenic mutation, P506T, and that the propensity of UBQLN2 to aggregate correlated with neurotoxicity. Here, we systematically assess the effects of multiple, spatially distinct ALS/FTD-linked missense mutations on UBQLN2 aggregation propensity, neurotoxicity, phase separation, and autophagic flux. In contrast to what we observed for the P506T mutation, no other tested pathogenic mutant exhibited a clear correlation between aggregation propensity and neurotoxicity. These results emphasize the unique nature of pathogenic UBQLN2 mutations and argue against a generalizable link between aggregation propensity and neurodegeneration in UBQLN2-linked ALS/FTD.

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Biomolecular condensates and disease pathogenesis

Ruan,

Bai,

Fang

et al. 2024

Sci. China Life Sci.

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The implications of physiological biomolecular condensates in amyotrophic lateral sclerosis

Cited by 9 publications

References 135 publications

Platinum-based drugs induce phenotypic alterations in nucleoli and Cajal bodies in prostate cancer cells

Platinum-based drugs induce phenotypic alterations in nucleoli and Cajal bodies in prostate cancer cells

Pathogenic mutations in UBQLN2 exhibit diverse aggregation propensity and neurotoxicity

Biomolecular condensates and disease pathogenesis

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