Distinct functions of <i>junD</i> in cardiac hypertrophy and heart failure

Ricci, Roméo; Eriksson, Urs; Oudit, Gavin Y.; Eferl, Robert; Akhmedov, Alexander; Sumara, Izabela; Sumara, Grzegorz; Kassiri, Zamaneh; David, Jean‐Pierre; Bakiri, Latifa; Sasse, Bernd; Idarraga, Maria-Helena; Rath, Martina; Kurz, David J.; Theussl, Hans-Christian; Perriard, Jean‐Claude; Backx, Peter H.; Penninger, Josef; Wagner, Erwin F.

doi:10.1101/gad.327005

Cited by 47 publications

(45 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…26 Studies with junD Ϫ/Ϫ mice and cells have revealed new physiological functions of JunD, including regulation of spermatogenesis, control of cell senescence and apoptosis, prevention of renal cell proliferation and hyperplasia, regulation of lymphocyte proliferation and differentiation, inhibition of tumor angiogenesis, and cardiac hypertrophy. [11][12][13][27][28][29] Our studies of junD Ϫ/Ϫ mice have provided direct evidence that JunD functions as a profibrogenic factor in diseased liver. Interestingly, this is in contrast with the apparently antifibrogenic function that JunD has in the kidney following partial nephrectomy.…”

Section: Discussionmentioning

confidence: 99%

JunD is a profibrogenic transcription factor regulated by Jun N-terminal kinase-independent phosphorylation

et al. 2006

View full text Add to dashboard Cite

A ctivated (or myofibroblastic) hepatic stellate cells (HSCs) are cellular mediators of liver fibrosis through their secretion of interstitial collagens and tissue inhibitor of metalloproteinase-1 (TIMP-1), 1,2 which is a broad specific inhibitor of the matrix metalloproteinases (MMPs) and prevents MMP-catalyzed degradation of interstitial collagens in order to promote collagen deposition. A second fibrogenic role identified for TIMP-1 is as a suppressor of HSC apoptosis. 3 TIMP-1 gene transcription is induced during culture activation of isolated HSCs and is under the control of regulatory elements in the TIMP-1 promoter including activator protein-1 (AP-1) and RUNX binding sites. [4][5][6][7]

show abstract

Section: Discussionmentioning

confidence: 99%

JunD is a profibrogenic transcription factor regulated by Jun N-terminal kinase-independent phosphorylation

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Although AP-1 is up-regulated during the early stages of the hypertrophic response, FOSL1 (fra-1) gene deletion failed to affect the hypertrophic response to chronic pressure overload or sustained ␤-adrenergic stimulation (9). In contrast, fra-1 overexpression resulted in premature decompensation.…”

Section: Traf3ip2 (Traf3 Interacting Protein 2; Previously Known As Cmentioning

confidence: 99%

Cardiac-restricted Overexpression of TRAF3 Interacting Protein 2 (TRAF3IP2) Results in Spontaneous Development of Myocardial Hypertrophy, Fibrosis, and Dysfunction

Manjunath

Yoshida²,

Valente

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

TRAF3IP2 (TRAF3 interacting protein 2; previously known as CIKS or Act1) is a key intermediate in the normal inflammatory response and the pathogenesis of various autoimmune and inflammatory diseases. Induction of TRAF3IP2 activates IB kinase (IKK)/NF-B, JNK/AP-1, and c/EBP␤ and stimulates the expression of various inflammatory mediators with negative myocardial inotropic effects. To investigate the role of TRAF3IP2 in heart disease, we generated a transgenic mouse model with cardiomyocyte-specific TRAF3IP2 overexpression (TRAF3IP2-Tg). Echocardiography, magnetic resonance imaging, and pressure-volume conductance catheterization revealed impaired cardiac function in 2-month-old male transgenic (Tg) mice as evidenced by decreased ejection fraction, stroke volume, cardiac output, and peak ejection rate. Moreover, the male Tg mice spontaneously developed myocardial hypertrophy (increased heart/body weight ratio, cardiomyocyte cross-sectional area, GATA4 induction, and fetal gene re-expression). Furthermore, TRAF3IP2 overexpression resulted in the activation of IKK/NF-B, JNK/AP-1, c/EBP␤, and p38 MAPK and induction of proinflammatory cytokines, chemokines, and extracellular matrix proteins in the heart. Although myocardial hypertrophy decreased with age, cardiac fibrosis (increased number of myofibroblasts and enhanced expression and deposition of fibrillar collagens) increased progressively. Despite these adverse changes, TRAF3IP2 overexpression did not result in cell death at any time period. Interestingly, despite increased mRNA expression, TRAF3IP2 protein levels and activation of its downstream signaling intermediates remained unchanged in the hearts of female Tg mice. The female Tg mice also failed to develop myocardial hypertrophy. In summary, these results demonstrate that overexpression of TRAF3IP2 in male mice is sufficient to induce myocardial hypertrophy, cardiac fibrosis, and contractile dysfunction.

show abstract

“…3) (339). JunD, although dispensable for development, has been shown to be involved in muscle differentiation (11) and has been implicated in the development of cardiac hypertrophy (263). The JunD phosphorylation and docking site sequences (Tables 1 and 2) are conserved in a shorter splice form of JunD, ⌬-JunD, which lacks the N-terminal menin interaction domain, suggesting that both JunD splice forms are under the control of JNK phosphorylation (339).…”

Section: Transcription Factors As Jnk Substratesmentioning

confidence: 99%

Uses for JNK: the Many and Varied Substrates of the c-Jun N-Terminal Kinases

Bogoyevitch

Kobe

2006

Microbiol Mol Biol Rev

518

477

View full text Add to dashboard Cite

SUMMARY The c-Jun N-terminal kinases (JNKs) are members of a larger group of serine/threonine (Ser/Thr) protein kinases from the mitogen-activated protein kinase family. JNKs were originally identified as stress-activated protein kinases in the livers of cycloheximide-challenged rats. Their subsequent purification, cloning, and naming as JNKs have emphasized their ability to phosphorylate and activate the transcription factor c-Jun. Studies of c-Jun and related transcription factor substrates have provided clues about both the preferred substrate phosphorylation sequences and additional docking domains recognized by JNK. There are now more than 50 proteins shown to be substrates for JNK. These include a range of nuclear substrates, including transcription factors and nuclear hormone receptors, heterogeneous nuclear ribonucleoprotein K, and the Pol I-specific transcription factor TIF-IA, which regulates ribosome synthesis. Many nonnuclear substrates have also been characterized, and these are involved in protein degradation (e.g., the E3 ligase Itch), signal transduction (e.g., adaptor and scaffold proteins and protein kinases), apoptotic cell death (e.g., mitochondrial Bcl2 family members), and cell movement (e.g., paxillin, DCX, microtubule-associated proteins, the stathmin family member SCG10, and the intermediate filament protein keratin 8). The range of JNK actions in the cell is therefore likely to be complex. Further characterization of the substrates of JNK should provide clearer explanations of the intracellular actions of the JNKs and may allow new avenues for targeting the JNK pathways with therapeutic agents downstream of JNK itself.

show abstract

Distinct functions of junD in cardiac hypertrophy and heart failure

Cited by 47 publications

References 34 publications

JunD is a profibrogenic transcription factor regulated by Jun N-terminal kinase-independent phosphorylation

JunD is a profibrogenic transcription factor regulated by Jun N-terminal kinase-independent phosphorylation

Cardiac-restricted Overexpression of TRAF3 Interacting Protein 2 (TRAF3IP2) Results in Spontaneous Development of Myocardial Hypertrophy, Fibrosis, and Dysfunction

Uses for JNK: the Many and Varied Substrates of the c-Jun N-Terminal Kinases

Contact Info

Product

Resources

About