Substantial CCT activity is required for cell cycle progression and cytoskeletal organization in mammalian cells

Julie Grantham; Karen I Brackley; Keith R Willison

doi:10.1016/j.yexcr.2006.03.028

Substantial CCT activity is required for cell cycle progression and cytoskeletal organization in mammalian cells

Exp Cell Res. 2006 Jul 15;312(12):2309-24. doi: 10.1016/j.yexcr.2006.03.028.

Authors

Julie Grantham¹, Karen I Brackley, Keith R Willison

Affiliation

¹ Cancer Research UK Centre for Cell and Molecular Biology, Chester Beatty Laboratories, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK. julie.grantham@molbio.gu.se

PMID: 16765944
DOI: 10.1016/j.yexcr.2006.03.028

Abstract

The chaperonin CCT hexadecamer is required for the folding of non-native actins and tubulins in eukaryotic cells. Among the consequences of greatly reducing CCT holocomplex levels in human cell lines by siRNA targeting are growth arrest and changes in cell morphology and motility. Less extensive reduction of CCT activity via microinjection of an inhibitory anti-CCT epsilon subunit monoclonal antibody, which alters the rates of substrate processing by CCT in vitro, causes a delay in cell cycle progression through G1/S phase in synchronized Swiss 3T3 cells. The degree of growth arrest strongly correlates with the extent of CCT depletion, indicating that full CCT activity is required for normal cell growth and division. Depletion of CCT does not affect actin polypeptide synthesis but causes a reduction in levels of native actin and perturbation of actin-based cell motility in BE cells. There are no large-scale effects on cytoplasmic protein synthesis or a general heat shock response during periods of low CCT activity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actin Cytoskeleton / metabolism
Actins / biosynthesis
Actins / metabolism
Animals
Antibodies, Monoclonal / pharmacology
Apoptosis / physiology
Cell Cycle / drug effects
Cell Cycle / physiology*
Cell Cycle Proteins / metabolism
Cell Line, Tumor
Cell Movement / physiology
Cell Proliferation
Chaperonin Containing TCP-1
Chaperonins / genetics
Chaperonins / immunology
Chaperonins / metabolism*
Cyclin E / biosynthesis
Cytoskeleton / drug effects
Cytoskeleton / metabolism*
HSP90 Heat-Shock Proteins / metabolism
HeLa Cells
Humans
Mice
Microtubules / metabolism
Polo-Like Kinase 1
Protein Biosynthesis / genetics
Protein Serine-Threonine Kinases / metabolism
Proto-Oncogene Proteins / metabolism
RNA, Small Interfering / genetics
Swiss 3T3 Cells
Tubulin / biosynthesis
Tubulin / metabolism

Substances

Actins
Antibodies, Monoclonal
CCT5 protein, human
Cell Cycle Proteins
Cyclin E
HSP90 Heat-Shock Proteins
Proto-Oncogene Proteins
RNA, Small Interfering
Tcp1 protein, mouse
Tubulin
Protein Serine-Threonine Kinases
Chaperonin Containing TCP-1
Chaperonins