Proteomics

Dataset Information

0

Somatic increase of CCT8 mimics proteostasis of human pluripotent stem cells and extends C. elegans lifespan


ABSTRACT: Human embryonic stem cells can replicate indefinitely while maintaining their undifferentiated state and, therefore, are immortal in culture. This capacity may demand avoidance of any imbalance in protein homeostasis (proteostasis) that would otherwise compromise stem cell identity. Here we show that human pluripotent stem cells exhibit enhanced assembly of the TRiC/CCT complex, a chaperonin that facilitates the folding of 10% of the proteome. We find that ectopic expression of a single subunit (CCT8) is sufficient to increase TRiC/CCT assembly. Moreover, increased TRiC/CCT complex is required to avoid aggregation of mutant Huntingtin protein. We further show that increased expression of CCT8 in somatic tissues extends Caenorhabditis elegans lifespan in a TRiC/CCT-dependent manner. Ectopic expression of CCT8 also ameliorates the age-associated demise of proteostasis and corrects proteostatic deficiencies in worm models of Huntington’s disease. Our results suggest proteostasis is a common principle that links organismal longevity with hESC immortality.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Embryonic Stem Cell

SUBMITTER: David Vilchez  

LAB HEAD: David Vilchez

PROVIDER: PXD005123 | Pride | 2017-03-23

REPOSITORIES: Pride

Dataset's files

Source:
altmetric image

Publications

Somatic increase of CCT8 mimics proteostasis of human pluripotent stem cells and extends C. elegans lifespan.

Noormohammadi Alireza A   Khodakarami Amirabbas A   Gutierrez-Garcia Ricardo R   Lee Hyun Ju HJ   Koyuncu Seda S   König Tim T   Schindler Christina C   Saez Isabel I   Fatima Azra A   Dieterich Christoph C   Vilchez David D  

Nature communications 20161128


Human embryonic stem cells can replicate indefinitely while maintaining their undifferentiated state and, therefore, are immortal in culture. This capacity may demand avoidance of any imbalance in protein homeostasis (proteostasis) that would otherwise compromise stem cell identity. Here we show that human pluripotent stem cells exhibit enhanced assembly of the TRiC/CCT complex, a chaperonin that facilitates the folding of 10% of the proteome. We find that ectopic expression of a single subunit  ...[more]

Similar Datasets

| S-EPMC5133698 | BioStudies
| S-EPMC8373342 | BioStudies
| S-EPMC3628893 | BioStudies
| S-EPMC6629582 | BioStudies
| S-EPMC7288733 | BioStudies
| S-EPMC5345702 | BioStudies
| S-EPMC4329143 | BioStudies
2018-05-16 | PXD007270 | Pride
| S-EPMC8344900 | BioStudies
| S-SCDT-EMBOR-2021-52905V1P | BioStudies