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Adult fibroblasts use aggresomes only in distinct cell-states.

ABSTRACT: The aggresome is a protein turnover system in which proteins are trafficked along microtubules to the centrosome for degradation. Despite extensive focus on aggresomes in immortalized cell lines, it remains unclear if the aggresome is conserved in all primary cells and all cell-states. Here we examined the aggresome in primary adult mouse dermal fibroblasts shifted into four distinct cell-states. We found that in response to proteasome inhibition, quiescent and immortalized fibroblasts formed aggresomes, whereas proliferating and senescent fibroblasts did not. Using this model, we generated a resource to provide a characterization of the proteostasis networks in which the aggresome is used and transcriptomic features associated with the presence or absence of aggresome formation. Using this resource, we validate a previously reported role for p38 MAPK signaling in aggresome formation and identify TAK1 as a novel driver of aggresome formation upstream of p38 MAPKs. Together, our data demonstrate that the aggresome is a non-universal protein degradation system which can be used cell-state specifically and provide a resource for studying aggresome formation and function.

SUBMITTER: Morrow CS

PROVIDER: S-EPMC9440096 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Adult fibroblasts use aggresomes only in distinct cell-states.

Morrow Christopher S CS Arndt Zachary P ZP Klosa Payton C PC Peng Bo B Zewdie Eden Y EY Benayoun Bérénice A BA Moore Darcie L DL

Scientific reports 20220902 1

The aggresome is a protein turnover system in which proteins are trafficked along microtubules to the centrosome for degradation. Despite extensive focus on aggresomes in immortalized cell lines, it remains unclear if the aggresome is conserved in all primary cells and all cell-states. Here we examined the aggresome in primary adult mouse dermal fibroblasts shifted into four distinct cell-states. We found that in response to proteasome inhibition, quiescent and immortalized fibroblasts formed ag ...[more]

PMID: 36056070

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Project description:BackgroundMany cancer patients initiate dietary supplement use after cancer diagnosis. How dietary supplement use contributes to the total nutrient intake among cancer survivors as compared with individuals without cancer needs to be determined.ObjectivesWe aimed to evaluate nutrient intakes from dietary supplements among cancer survivors in relation to their total nutrient intake and compare those with individuals without cancer.MethodsWe evaluated the prevalence, dose, and reason for using dietary supplements among 2772 adult cancer survivors and 31,310 individuals without cancer who participated in the NHANES 2003-2016.ResultsCancer survivors reported a higher prevalence of any (70.4% vs. 51.2%) and multivitamin/mineral (48.9% vs. 36.6%) supplement use and supplement use of 11 individual vitamins and 8 minerals than individuals without cancer. Overall, cancer survivors had significantly higher amounts of nutrient intake from supplements but lower nutrient intakes from foods for the majority of the nutrients. Compared with individuals without cancer, cancer survivors had a higher percentage of individuals with inadequate intake (total nutrient intake <Estimated Average Requirement or Adequate Intake) for folate, vitamin B-6, niacin, calcium, copper, and phosphorus, due to lower intakes of these nutrients from foods. Cancer survivors also had a higher proportion of individuals with excess intake (total nutrient intake ≥Tolerable Upper Intake Level) for vitamin D, vitamin B-6, niacin, calcium, magnesium, and zinc, contributed by higher intakes of these nutrients from dietary supplements. Nearly half (46.1%) used dietary supplements on their own without consulting health care providers.ConclusionsCancer survivors reported a higher prevalence and dose of dietary supplement use but lower amounts of nutrient intake from foods than individuals without cancer. The inadequate nutrient intake from foods and the short-term and long-term health impact of dietary supplement use, especially at high doses, need to be further evaluated among cancer survivors.

Dataset Information

Adult fibroblasts use aggresomes only in distinct cell-states.

Publications

Adult fibroblasts use aggresomes only in distinct cell-states.

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