Maintenance of muscle myosin levels in adult C. elegans requires both the double bromodomain protein BET-1 and sumoylation.
Attenuation of RAS-mediated signalling is a conserved process essential to control cell proliferation, differentiation, and apoptosis. Cooperative interactions between histone modifications such as acetylation, methylation and sumoylation are crucial for proper attenuation in C. elegans, implying th...
Main Authors: | , , , , , , , , , , |
---|---|
Format: | Journal article |
Language: | English |
Published: |
2013
|
_version_ | 1797060922699677696 |
---|---|
author | Fisher, K Gee, F Wang, S Xue, F Knapp, S Philpott, M Wells, C Rodriguez, M Snoek, L Kammenga, J Poulin, G |
author_facet | Fisher, K Gee, F Wang, S Xue, F Knapp, S Philpott, M Wells, C Rodriguez, M Snoek, L Kammenga, J Poulin, G |
author_sort | Fisher, K |
collection | OXFORD |
description | Attenuation of RAS-mediated signalling is a conserved process essential to control cell proliferation, differentiation, and apoptosis. Cooperative interactions between histone modifications such as acetylation, methylation and sumoylation are crucial for proper attenuation in C. elegans, implying that the proteins recognising these histone modifications could also play an important role in attenuation of RAS-mediated signalling. We sought to systematically identify these proteins and found BET-1. BET-1 is a conserved double bromodomain protein that recognises acetyl-lysines on histone tails and maintains the stable fate of various lineages. Unexpectedly, adults lacking both BET-1 and SUMO-1 are depleted of muscle myosin, an essential component of myofibrils. We also show that this muscle myosin depletion does not occur in all animals at a specific time, but rather that the penetrance of the phenotype increases with age. To gain mechanistic insights into this process, we sought to delay the occurrence of the muscle myosin depletion phenotype and found that it requires caspase activity and MEK-dependent signalling. We also performed transcription profiling on these mutants and found an up-regulation of the FGF receptor, egl-15, a tyrosine kinase receptor acting upstream of MEK. Consistent with a MEK requirement, we could delay the muscle phenotype by systemic or hypodermal knock down of egl-15. Thus, this work uncovered a caspase- and MEK-dependent mechanism that acts specifically on ageing adults to maintain the appropriate net level of muscle myosin. |
first_indexed | 2024-03-06T20:23:44Z |
format | Journal article |
id | oxford-uuid:2eb2bf3f-417c-4eb9-983b-aa8bfd857039 |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-06T20:23:44Z |
publishDate | 2013 |
record_format | dspace |
spelling | oxford-uuid:2eb2bf3f-417c-4eb9-983b-aa8bfd8570392022-03-26T12:50:31ZMaintenance of muscle myosin levels in adult C. elegans requires both the double bromodomain protein BET-1 and sumoylation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2eb2bf3f-417c-4eb9-983b-aa8bfd857039EnglishSymplectic Elements at Oxford2013Fisher, KGee, FWang, SXue, FKnapp, SPhilpott, MWells, CRodriguez, MSnoek, LKammenga, JPoulin, GAttenuation of RAS-mediated signalling is a conserved process essential to control cell proliferation, differentiation, and apoptosis. Cooperative interactions between histone modifications such as acetylation, methylation and sumoylation are crucial for proper attenuation in C. elegans, implying that the proteins recognising these histone modifications could also play an important role in attenuation of RAS-mediated signalling. We sought to systematically identify these proteins and found BET-1. BET-1 is a conserved double bromodomain protein that recognises acetyl-lysines on histone tails and maintains the stable fate of various lineages. Unexpectedly, adults lacking both BET-1 and SUMO-1 are depleted of muscle myosin, an essential component of myofibrils. We also show that this muscle myosin depletion does not occur in all animals at a specific time, but rather that the penetrance of the phenotype increases with age. To gain mechanistic insights into this process, we sought to delay the occurrence of the muscle myosin depletion phenotype and found that it requires caspase activity and MEK-dependent signalling. We also performed transcription profiling on these mutants and found an up-regulation of the FGF receptor, egl-15, a tyrosine kinase receptor acting upstream of MEK. Consistent with a MEK requirement, we could delay the muscle phenotype by systemic or hypodermal knock down of egl-15. Thus, this work uncovered a caspase- and MEK-dependent mechanism that acts specifically on ageing adults to maintain the appropriate net level of muscle myosin. |
spellingShingle | Fisher, K Gee, F Wang, S Xue, F Knapp, S Philpott, M Wells, C Rodriguez, M Snoek, L Kammenga, J Poulin, G Maintenance of muscle myosin levels in adult C. elegans requires both the double bromodomain protein BET-1 and sumoylation. |
title | Maintenance of muscle myosin levels in adult C. elegans requires both the double bromodomain protein BET-1 and sumoylation. |
title_full | Maintenance of muscle myosin levels in adult C. elegans requires both the double bromodomain protein BET-1 and sumoylation. |
title_fullStr | Maintenance of muscle myosin levels in adult C. elegans requires both the double bromodomain protein BET-1 and sumoylation. |
title_full_unstemmed | Maintenance of muscle myosin levels in adult C. elegans requires both the double bromodomain protein BET-1 and sumoylation. |
title_short | Maintenance of muscle myosin levels in adult C. elegans requires both the double bromodomain protein BET-1 and sumoylation. |
title_sort | maintenance of muscle myosin levels in adult c elegans requires both the double bromodomain protein bet 1 and sumoylation |
work_keys_str_mv | AT fisherk maintenanceofmusclemyosinlevelsinadultcelegansrequiresboththedoublebromodomainproteinbet1andsumoylation AT geef maintenanceofmusclemyosinlevelsinadultcelegansrequiresboththedoublebromodomainproteinbet1andsumoylation AT wangs maintenanceofmusclemyosinlevelsinadultcelegansrequiresboththedoublebromodomainproteinbet1andsumoylation AT xuef maintenanceofmusclemyosinlevelsinadultcelegansrequiresboththedoublebromodomainproteinbet1andsumoylation AT knapps maintenanceofmusclemyosinlevelsinadultcelegansrequiresboththedoublebromodomainproteinbet1andsumoylation AT philpottm maintenanceofmusclemyosinlevelsinadultcelegansrequiresboththedoublebromodomainproteinbet1andsumoylation AT wellsc maintenanceofmusclemyosinlevelsinadultcelegansrequiresboththedoublebromodomainproteinbet1andsumoylation AT rodriguezm maintenanceofmusclemyosinlevelsinadultcelegansrequiresboththedoublebromodomainproteinbet1andsumoylation AT snoekl maintenanceofmusclemyosinlevelsinadultcelegansrequiresboththedoublebromodomainproteinbet1andsumoylation AT kammengaj maintenanceofmusclemyosinlevelsinadultcelegansrequiresboththedoublebromodomainproteinbet1andsumoylation AT pouling maintenanceofmusclemyosinlevelsinadultcelegansrequiresboththedoublebromodomainproteinbet1andsumoylation |