Phosphorylation of the Twist1-family basic helix-loop-helix transcription factors is involved in pathological cardiac remodeling.
The Twist1-family basic helix-loop-helix (bHLH) transcription factors including Twist1, Hand1 and Hand2, play an essential role in heart development and are implicated in pathological heart remodeling. Previously, it was reported that these bHLH transcription factors can be regulated by phosphorylat...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-04-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3084786?pdf=render |
| _version_ | 1811281976596889600 |
|---|---|
| author | Shuangshuang Lu Junwei Nie Qing Luan Qiuting Feng Qi Xiao Zai Chang Congjia Shan Daniel Hess Brian A Hemmings Zhongzhou Yang |
| author_facet | Shuangshuang Lu Junwei Nie Qing Luan Qiuting Feng Qi Xiao Zai Chang Congjia Shan Daniel Hess Brian A Hemmings Zhongzhou Yang |
| author_sort | Shuangshuang Lu |
| collection | DOAJ |
| description | The Twist1-family basic helix-loop-helix (bHLH) transcription factors including Twist1, Hand1 and Hand2, play an essential role in heart development and are implicated in pathological heart remodeling. Previously, it was reported that these bHLH transcription factors can be regulated by phosphorylation within the basic-helix I domain, which is involved in developmental processes such as limb formation and trophoblast differentiation. However, how phosphorylation of Twist1 family functions in post-natal heart is elusive.Here, we generated transgenic mice with over-expression of Hand1 and Twist1 mutants (to mimic or to abolish phosphorylation) in cardiomyocytes and found pathological cardiac remodeling leading to heart failure and sudden death. Gene expression profile analysis revealed up-regulation of growth-promoting genes and down-regulation of metabolic genes. It is well known that aberrant activation of Akt signaling causes pathological cardiac remodeling and results in heart failure. The basic-helix I domain of Twist1 family members contain Akt substrate consensus motif and may be downstream targets of Akt signaling. Using biochemical analysis, we demonstrated that Hand1 and Twist1 were phosphorylated by Akt in the basic-helix I domain. Phosphorylation of Hand1 regulated its transcriptional activation of luciferase reporter genes and DNA binding ability.This study provides novel insights into the regulation of Twist1 family in cardiac remodeling and suggests that the Twist1 family can be regulated by Akt signaling. |
| first_indexed | 2024-04-13T01:43:21Z |
| format | Article |
| id | doaj.art-aadb5c04ff40448f9578148357bf2e49 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T01:43:21Z |
| publishDate | 2011-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-aadb5c04ff40448f9578148357bf2e492022-12-22T03:08:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-04-0164e1925110.1371/journal.pone.0019251Phosphorylation of the Twist1-family basic helix-loop-helix transcription factors is involved in pathological cardiac remodeling.Shuangshuang LuJunwei NieQing LuanQiuting FengQi XiaoZai ChangCongjia ShanDaniel HessBrian A HemmingsZhongzhou YangThe Twist1-family basic helix-loop-helix (bHLH) transcription factors including Twist1, Hand1 and Hand2, play an essential role in heart development and are implicated in pathological heart remodeling. Previously, it was reported that these bHLH transcription factors can be regulated by phosphorylation within the basic-helix I domain, which is involved in developmental processes such as limb formation and trophoblast differentiation. However, how phosphorylation of Twist1 family functions in post-natal heart is elusive.Here, we generated transgenic mice with over-expression of Hand1 and Twist1 mutants (to mimic or to abolish phosphorylation) in cardiomyocytes and found pathological cardiac remodeling leading to heart failure and sudden death. Gene expression profile analysis revealed up-regulation of growth-promoting genes and down-regulation of metabolic genes. It is well known that aberrant activation of Akt signaling causes pathological cardiac remodeling and results in heart failure. The basic-helix I domain of Twist1 family members contain Akt substrate consensus motif and may be downstream targets of Akt signaling. Using biochemical analysis, we demonstrated that Hand1 and Twist1 were phosphorylated by Akt in the basic-helix I domain. Phosphorylation of Hand1 regulated its transcriptional activation of luciferase reporter genes and DNA binding ability.This study provides novel insights into the regulation of Twist1 family in cardiac remodeling and suggests that the Twist1 family can be regulated by Akt signaling.http://europepmc.org/articles/PMC3084786?pdf=render |
| spellingShingle | Shuangshuang Lu Junwei Nie Qing Luan Qiuting Feng Qi Xiao Zai Chang Congjia Shan Daniel Hess Brian A Hemmings Zhongzhou Yang Phosphorylation of the Twist1-family basic helix-loop-helix transcription factors is involved in pathological cardiac remodeling. PLoS ONE |
| title | Phosphorylation of the Twist1-family basic helix-loop-helix transcription factors is involved in pathological cardiac remodeling. |
| title_full | Phosphorylation of the Twist1-family basic helix-loop-helix transcription factors is involved in pathological cardiac remodeling. |
| title_fullStr | Phosphorylation of the Twist1-family basic helix-loop-helix transcription factors is involved in pathological cardiac remodeling. |
| title_full_unstemmed | Phosphorylation of the Twist1-family basic helix-loop-helix transcription factors is involved in pathological cardiac remodeling. |
| title_short | Phosphorylation of the Twist1-family basic helix-loop-helix transcription factors is involved in pathological cardiac remodeling. |
| title_sort | phosphorylation of the twist1 family basic helix loop helix transcription factors is involved in pathological cardiac remodeling |
| url | http://europepmc.org/articles/PMC3084786?pdf=render |
| work_keys_str_mv | AT shuangshuanglu phosphorylationofthetwist1familybasichelixloophelixtranscriptionfactorsisinvolvedinpathologicalcardiacremodeling AT junweinie phosphorylationofthetwist1familybasichelixloophelixtranscriptionfactorsisinvolvedinpathologicalcardiacremodeling AT qingluan phosphorylationofthetwist1familybasichelixloophelixtranscriptionfactorsisinvolvedinpathologicalcardiacremodeling AT qiutingfeng phosphorylationofthetwist1familybasichelixloophelixtranscriptionfactorsisinvolvedinpathologicalcardiacremodeling AT qixiao phosphorylationofthetwist1familybasichelixloophelixtranscriptionfactorsisinvolvedinpathologicalcardiacremodeling AT zaichang phosphorylationofthetwist1familybasichelixloophelixtranscriptionfactorsisinvolvedinpathologicalcardiacremodeling AT congjiashan phosphorylationofthetwist1familybasichelixloophelixtranscriptionfactorsisinvolvedinpathologicalcardiacremodeling AT danielhess phosphorylationofthetwist1familybasichelixloophelixtranscriptionfactorsisinvolvedinpathologicalcardiacremodeling AT brianahemmings phosphorylationofthetwist1familybasichelixloophelixtranscriptionfactorsisinvolvedinpathologicalcardiacremodeling AT zhongzhouyang phosphorylationofthetwist1familybasichelixloophelixtranscriptionfactorsisinvolvedinpathologicalcardiacremodeling |