Adaptor proteins NUMB and NUMBL promote cell cycle withdrawal by targeting ERBB2 for degradation

Hirai, Masana; Arita, Yoh; McGlade, C. Jane; Lee, Kuo‐Fen; Chen, Ju; Evans, Sylvia M.

doi:10.1172/jci91081

Cited by 44 publications

(48 citation statements)

References 59 publications

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“…After blocking for 1 hour in TBS containing 0.1% Tween-20 (TBST) and 5% dry milk, the membranes were incubated overnight at 4°C with the indicated primary antibody (listed in Supplemental Table 2) in blocking buffer containing 2% dry milk. Blots were washed and incubated with HRP-conjugated secondary antibody generated in rabbit (1:5,000) or mouse (1:2,000) (Dako) for 1 hour at room temperature (66). Immunoreactive protein bands were visualized using ECL reagent (Thermo Fisher Scientific).…”

Section: Author Contributionsmentioning

confidence: 99%

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Loss-of-function mutations in co-chaperone BAG3 destabilize small HSPs and cause cardiomyopathy

Fang

Bogomolovas

et al. 2017

Journal of Clinical Investigation

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116

154

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Section: Author Contributionsmentioning

confidence: 99%

“…Hearts were subsequently dehydrated in 70% ethanol, embedded in paraffin, and coronally sectioned (10-μm thickness). Sections were stained with Masson's trichrome or H&E as previously described (65,66) and then mounted and imaged using a Hamamatsu NanoZoomer 2.0HT Slide Scanning System.…”

Section: Author Contributionsmentioning

confidence: 99%

Loss-of-function mutations in co-chaperone BAG3 destabilize small HSPs and cause cardiomyopathy

Fang

Bogomolovas

et al. 2017

Journal of Clinical Investigation

Self Cite

116

154

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“…Altered cellular shape, connectivity and adhesion, actin dynamics, and the continuum between the cytoskeleton and the nucleus via the 'Linker of Nucleoskeleton and Cytoskeleton' complex (LINC complex), are all implicated in mechanotransduction signaling. Numerous studies demonstrated a Hippo-independent YAP regulation, highlighting a multifaceted control of YAP, especially in the heart (Ragni et al, 2017) (Hirai et al, 2017) .…”

Section: Introductionmentioning

confidence: 99%

ERBB2 drives YAP activation and EMT-like processes during cardiac regeneration

Aharonov

Shakked

Umansky

et al. 2020

Preprint

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Cardiomyocyte (CM) loss after injury results in adverse remodelling and fibrosis, which inevitably lead to heart failure. ERBB2-Neuregulin and Hippo-YAP signaling pathways are key mediators of CM proliferation and regeneration, yet the crosstalk between these pathways is unclear. Here, we demonstrate in adult mice that transient over-expression (OE) of activated ERBB2 in CMs promotes cardiac regeneration in a heart failure model. OE CMs present an EMT-like regenerative response manifested by cytoskeletal remodelling, junction dissolution, migration, and ECM turnover. Molecularly, we identified YAP as a critical mediator of ERBB2 signaling. In OE CMs, YAP interacts with nuclear envelope and cytoskeletal components, reflecting the altered mechanic state elicited by ERBB2. Hippoindependent activating phosphorylation on YAP at S352 and S274 were enriched in OE CMs, peaking during metaphase, and viral overexpression of YAP phospho-mutants dampened the proliferative competence of OE CMs. Taken together, we demonstrate a potent ERBB2mediated YAP mechanosensory signaling, involving EMT-like characteristics, resulting in heart regeneration. Highlights1. ERBB2-driven regeneration of scarred hearts recapitulates core-EMT processes 2. YAP is activated and required downstream to ERBB2 signaling in CMs 3. YAP activity is mechanically driven by cytoskeleton and nuclear envelope remodeling 4. YAP S274 and S352 phosphorylation is essential for CM mitosis

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“…Advances in molecular and genetic techniques have vastly improved the understanding of molecular mechanisms responsible for cardiomyopathies and cardiac Table 6. Animal models of left ventricular noncompaction cardiomyopathy [141][142][143][144][145][146][147][148][149][150][151][152][153][154][155][156][157][158][159]. DOI: http://dx.doi.org/10.5772/intechopen.89033 dysfunction.…”

Section: Resultsmentioning

confidence: 99%

Animal Models of Cardiomyopathies

Purevjav¹

2020

Animal Models in Medicine and Biology

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Cardiomyopathies are a heterogeneous group of disorders of heart muscle that ultimately result in congestive heart failure (CHF). Rapid progress in genetics as well as in molecular and cellular biology over the past three decades has greatly improved the understanding of pathogenic signaling pathways in inherited cardiomyopathies. This chapter will focus on animal models of different clinical forms of human cardiomyopathies with their summaries of triggered key molecules, and signaling pathways will be described.

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Adaptor proteins NUMB and NUMBL promote cell cycle withdrawal by targeting ERBB2 for degradation

Cited by 44 publications

References 59 publications

Loss-of-function mutations in co-chaperone BAG3 destabilize small HSPs and cause cardiomyopathy

Loss-of-function mutations in co-chaperone BAG3 destabilize small HSPs and cause cardiomyopathy

ERBB2 drives YAP activation and EMT-like processes during cardiac regeneration

Animal Models of Cardiomyopathies

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