negative regulation of cell growth involved in cardiac muscle cell development

Definition

Target type: biologicalprocess

Any process that decreases the rate, frequency, or extent of the growth of a cardiac muscle cell, where growth contributes to the progression of the cell over time from its initial formation to its mature state. [GOC:dph]

Cardiac muscle cell development, a complex process involving precise coordination of cell proliferation, differentiation, and survival, is tightly regulated by intricate signaling networks. Negative regulation of cell growth plays a pivotal role in ensuring proper heart development. This regulation involves a delicate balance of pro- and anti-growth factors, signaling pathways, and transcription factors. Key players include:

**1. TGF-beta Family:** Transforming Growth Factor beta (TGF-beta) signaling, notably through the Smad pathway, is a potent negative regulator of cardiac cell proliferation. TGF-beta isoforms, such as TGF-beta1, are secreted in a latent form and activated upon injury or stress. Once activated, TGF-beta binds to its receptor complex, initiating a phosphorylation cascade leading to the activation of Smad2 and Smad3. These activated Smads translocate to the nucleus and associate with other transcription factors to regulate the expression of target genes involved in cell cycle arrest and apoptosis, ultimately suppressing cell growth.

**2. Wnt Signaling:** The Wnt signaling pathway, particularly the canonical Wnt pathway, exhibits dual roles in cardiac development, promoting cell proliferation at early stages while inhibiting growth at later stages. In the context of negative regulation, Wnt signaling, through activation of downstream transcription factors like TCF/LEF, can induce the expression of genes involved in cell cycle arrest and differentiation, contributing to the transition from proliferation to maturation.

**3. Hippo Signaling:** The Hippo signaling pathway, a key regulator of organ size and cell proliferation, exerts significant negative control over cardiac development. The core components of the Hippo pathway, including the kinases MST1/2 and LATS1/2, are activated in response to cell density or mechanical cues. Activated LATS1/2 phosphorylate and inhibit the transcriptional co-activators YAP and TAZ, preventing their nuclear translocation. In the nucleus, YAP and TAZ promote cell proliferation and survival, while their inhibition by Hippo signaling promotes cell cycle arrest and apoptosis, thereby controlling cell growth.

**4. Notch Signaling:** The Notch signaling pathway, primarily through its activation by ligands like Delta-like 1 (Dll1) and Jagged1, plays a crucial role in regulating cell fate decisions during heart development. Notch activation leads to the proteolytic cleavage of Notch receptor, generating an intracellular domain that translocates to the nucleus and activates target genes involved in differentiation and cell cycle arrest. By promoting differentiation and suppressing proliferation, Notch signaling contributes to the negative regulation of cell growth in cardiac muscle development.

**5. MicroRNAs:** MicroRNAs (miRNAs), small non-coding RNAs, are essential regulators of gene expression and play crucial roles in cardiac development. Specific miRNAs, like miR-21, miR-22, and miR-26, have been shown to negatively regulate cell growth by targeting genes involved in cell cycle progression and proliferation, contributing to the fine-tuning of cardiac cell development.'
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Proteins (4)

Compounds (431)