Universität zu Köln

Noormohammadi, Alireza, Khodakarami, Amirabbas, Gutierrez-Garcia, Ricardo, Lee, Hyun Ju, Koyuncu, Seda, Nig, Tim Ko, Schindler, Christina, Saez, Isabel, Fatima, Azra, Dieterich, Christoph and Vilchez, David ORCID: 0000-0002-0801-0743 (2016). Somatic increase of CCT8 mimics proteostasis of human pluripotent stem cells and extends C-elegans lifespan. Nat. Commun., 7. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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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/CCTcomplex 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Noormohammadi, Alireza UNSPECIFIED UNSPECIFIED UNSPECIFIED Khodakarami, Amirabbas UNSPECIFIED UNSPECIFIED UNSPECIFIED Gutierrez-Garcia, Ricardo UNSPECIFIED UNSPECIFIED UNSPECIFIED Lee, Hyun Ju UNSPECIFIED UNSPECIFIED UNSPECIFIED Koyuncu, Seda UNSPECIFIED UNSPECIFIED UNSPECIFIED Nig, Tim Ko UNSPECIFIED UNSPECIFIED UNSPECIFIED Schindler, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Saez, Isabel UNSPECIFIED UNSPECIFIED UNSPECIFIED Fatima, Azra UNSPECIFIED UNSPECIFIED UNSPECIFIED Dieterich, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Vilchez, David UNSPECIFIED orcid.org/0000-0002-0801-0743 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-255377
DOI:	10.1038/ncomms13649
Journal or Publication Title:	Nat. Commun.
Volume:	7
Date:	2016
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2041-1723
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CAENORHABDITIS-ELEGANS; PROTEASOME ACTIVITY; EXPRESSION ANALYSIS; CHAPERONIN; PROTEIN; GENE; DISEASES; QUANTIFICATION; PROLIFERATION; AGGREGATION Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/25537