2026-06-14T17:49:50Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/52502024-09-27T08:00:59Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605col_20.500.12105_19607
Repisalud
author
Gonzalez-Teran, Barbara
author
Lopez, Juan Antonio
author
Rodriguez, Elena
author
Leiva-Vega, Luis
author
Martinez-Martinez, Sara
author
Bernal, Juan Antonio
author
Jimenez-Borreguero, Luis J.
author
Redondo, Juan Miguel
author
Vazquez, Jesus
author
Sabio, Guadalupe
funder
Ministerio de Economía y Competitividad (España)
funder
Unión Europea. Comisión Europea
funder
European Foundation for the Study of Diabetes
funder
Ministerio de Ciencia e Innovación (España)
funder
Comunidad de Madrid (España)
funder
Red de Investigación Cardiovascular (RIC) (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Fundación La Marató TV3
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Fundación ProCNIC
2017-10-30T13:32:27Z
2017-10-30T13:32:27Z
2016
Nat Commun. 2016; 7:10477
10.1038/ncomms10477
2041-1723
Nature Communications
26795633
http://hdl.handle.net/20.500.12105/5250
Disrupted organ growth leads to disease development. Hypertrophy underlies postnatal heart growth and is triggered after stress, but the molecular mechanisms involved in these processes are largely unknown. Here we show that cardiac activation of p38 gamma and p38 delta increases during postnatal development and by hypertrophy-inducing stimuli. p38 gamma/delta promote cardiac hypertrophy by phosphorylating the mTORC1 and mTORC2 inhibitor DEPTOR, which leads to its degradation and mTOR activation. Hearts from mice lacking one or both kinases are below normal size, have high levels of DEPTOR, low activity of the mTOR pathway and reduced protein synthesis. The phenotype of p38 gamma/delta(-/-) mice is reverted by overactivation of mTOR with amino acids, shRNA-mediated knockdown of Deptor, or cardiomyocyte overexpression of active p38 gamma and p38 delta. Moreover, in WT mice, heart weight is reduced by cardiac overexpression of DEPTOR. Our results demonstrate that p38 gamma/delta control heart growth by modulating mTOR pathway through DEPTOR phosphorylation and subsequent degradation.
eng
INDUCED CARDIAC-HYPERTROPHY
SIGNALING PATHWAYS
PRESSURE-OVERLOAD
UBIQUITIN LIGASE
ANGIOTENSIN-II
KINASE PLAYS
S6 KINASE
P38
MICE
CARDIOMYOPATHY
p38 gamma and delta promote heart hypertrophy by targeting the mTOR-inhibitory protein DEPTOR for degradation
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P38gammaAndDeltaPromote_2016
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P38gammaAndDeltaPromote_2016.txt