Depletion of MOB1A/B causes intestinal epithelial degeneration by suppressing Wnt activity and activating BMP/TGF-β signaling

Bae, June Sung; Jeon, Yongseok; Kim, Sun Mi; Jang, Ji Yun; Park, Mi Kyung; Kim, In-Hoo; Hwang, Deog Su; Lim, Dae‐Sik; Lee, Ho

doi:10.1038/s41419-018-1138-0

Cited by 19 publications

(23 citation statements)

References 56 publications

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“…Bae et al [59] investigated the relationship between Hippo and other signaling pathways including EGF signaling and the role of Mps one binder (MOB) kinase activator 1A/1B (MOB1A/B) in intestinal homeostasis. MOB1A/B is a core component of the Hippo signaling pathway, which plays a crucial role in cell proliferation, apoptosis, differentiation, and development.…”

Section: Epidermal Growth Factor (Egf) Signalingmentioning

confidence: 99%

“…MOB1A/B binds to and activates large tumor suppressor 1 and 2 (LATS1/2) kinase, followed by phosphorylation of YAP. Bae et al discovered that loss of MOB1A/B in intestinal epithelial cells reduces the expression of ISC niche factors including EGF [59]. However, other EGF receptor (EGFR) ligands, including amphiregulin (Areg) and epiregulin (Ereg), are markedly upregulated in intestinal epithelial cells of MOB1A/B-deficient mice [59].…”

Section: Epidermal Growth Factor (Egf) Signalingmentioning

confidence: 99%

“…Bae et al discovered that loss of MOB1A/B in intestinal epithelial cells reduces the expression of ISC niche factors including EGF [59]. However, other EGF receptor (EGFR) ligands, including amphiregulin (Areg) and epiregulin (Ereg), are markedly upregulated in intestinal epithelial cells of MOB1A/B-deficient mice [59]. Areg and Ereg transcription can be induced by YAP or transcriptional co-activator with PDZ-binding motif (TAZ) activity [60,61], and thus, their results support the notion that EGF signaling interacts with Hippo signaling.…”

Section: Epidermal Growth Factor (Egf) Signalingmentioning

confidence: 99%

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Stem Cell Signaling Pathways in the Small Intestine

Takahashi

Shiraishi

2020

IJMS

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The ability of stem cells to divide and differentiate is necessary for tissue repair and homeostasis. Appropriate spatial and temporal mechanisms are needed. Local intercellular signaling increases expression of specific genes that mediate and maintain differentiation. Diffusible signaling molecules provide concentration-dependent induction of specific patterns of cell types or regions. Differentiation of adjacent cells, on the other hand, requires cell–cell contact and subsequent signaling. These two types of signals work together to allow stem cells to provide what organisms require. The ability to grow organoids has increased our understanding of the cellular and molecular features of small “niches” that modulate stem cell function in various organs, including the small intestine.

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Section: Epidermal Growth Factor (Egf) Signalingmentioning

confidence: 99%

Section: Epidermal Growth Factor (Egf) Signalingmentioning

confidence: 99%

Section: Epidermal Growth Factor (Egf) Signalingmentioning

confidence: 99%

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Stem Cell Signaling Pathways in the Small Intestine

Takahashi

Shiraishi

2020

IJMS

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“…In colorectal cancer, β‐catenin was shown to directly induce Yap expression, suggesting a positive feedback loop that reinforces Yap and β‐catenin target gene induction (Konsavage, Kyler, Rennoll, Jin, & Yochum, ). Finally, the adaptor protein Mob1A/B was found to regulate Wnt target gene expression in a Yap‐dependent manner in the intestinal epithelium, such that Mob1A/B depletion resulted in the ablation of the intestinal stem cell pool, although a molecular mechanism was not described (Bae et al, ). Together these studies demonstrate extensive Hippo‐Wnt crosstalk during both active and inactive Wnt signaling.…”

Section: Cooperation Between Hippo‐yap/taz Signaling and Intracellulamentioning

confidence: 99%

Hippo‐Yap/Taz signaling: Complex network interactions and impact in epithelial cell behavior

Soldt

Cardoso

2019

WIREs Developmental Biology

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The Hippo pathway has emerged as a crucial integrator of signals in biological events from development to adulthood and in diseases. Although extensively studied in Drosophila and in cell cultures, major gaps of knowledge still remain on how this pathway functions in mammalian systems. The pathway consists of a growing number of components, including core kinases and adaptor proteins, which control the subcellular localization of the transcriptional co‐activators Yap and Taz through phosphorylation of serines at key sites. When localized to the nucleus, Yap/Taz interact with TEAD transcription factors to induce transcriptional programs of proliferation, stemness, and growth. In the cytoplasm, Yap/Taz interact with multiple pathways to regulate a variety of cellular functions or are targeted for degradation. The Hippo pathway receives cues from diverse intracellular and extracellular inputs, including growth factor and integrin signaling, polarity complexes, and cell–cell junctions. This review highlights the mechanisms of regulation of Yap/Taz nucleocytoplasmic shuttling and their implications for epithelial cell behavior using the lung as an intriguing example of this paradigm. This article is categorized under: Gene Expression and Transcriptional Hierarchies > Regulatory Mechanisms Signaling Pathways > Cell Fate Signaling Establishment of Spatial and Temporal Patterns > Cytoplasmic Localization

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“…1. Targeting strategies of Mob1a flox and Mob1b flox alleles were performed as described previously 39 and in Supplementary Fig. 2.…”

Section: Generation Of Mob1a and Mob1b Knockout Mousementioning

confidence: 99%

Loss of Mob1a/b impairs the differentiation of mouse embryonic stem cells into the three germ layer lineages

et al. 2019

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The Hippo pathway plays a crucial role in cell proliferation and apoptosis and can regulate stem cell maintenance and embryonic development. MOB kinase activators 1A and 1B (Mob1a/b) are key components of the Hippo pathway, whose homozygous deletion in mice causes early embryonic lethality at the preimplantation stage. To investigate the role of Mob1a/b in stem cell maintenance and differentiation, an embryonic stem cell (ESC) clone in which Mob1a/b could be conditionally depleted was generated and characterized. Although Mob1a/b depletion did not affect the stemness or proliferation of mouse ESCs, this depletion caused defects in differentiation into the three germ layers. Yap knockdown rescued the in vitro and in vivo defects in differentiation caused by Mob1a/b depletion, suggesting that differentiation defects caused by Mob1a/b depletion were Yap-dependent. In teratoma experiments, Yap knockdown in Mob1a/b-depleted ESCs partially restored defects in differentiation, indicating that hyperactivation of Taz, another effector of the Hippo pathway, inhibited differentiation into the three germ layers. Taken together, these results suggest that Mob1a/b or Hippo signaling plays a critical role in the differentiation of mouse ESCs into the three germ layers, which is dependent on Yap. These close relationship of the Hippo pathway with the differentiation of stem cells supports its potential as a therapeutic target in regenerative medicine.

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Depletion of MOB1A/B causes intestinal epithelial degeneration by suppressing Wnt activity and activating BMP/TGF-β signaling

Cited by 19 publications

References 56 publications

Stem Cell Signaling Pathways in the Small Intestine

Stem Cell Signaling Pathways in the Small Intestine

Hippo‐Yap/Taz signaling: Complex network interactions and impact in epithelial cell behavior

Loss of Mob1a/b impairs the differentiation of mouse embryonic stem cells into the three germ layer lineages

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