constitutive protein ectodomain proteolysis

Definition

Target type: biologicalprocess

The proteolytic cleavage of transmembrane proteins and release of their ectodomain that occurs constantly, regardless of environmental conditions or demands. [PMID:12714508]

Constitutive protein ectodomain proteolysis is a fundamental cellular process that involves the regulated cleavage of proteins at their extracellular domains. This process plays a crucial role in a wide range of biological functions, including cell signaling, cell adhesion, and matrix remodeling. Unlike regulated proteolysis, which is typically triggered by specific stimuli, constitutive proteolysis occurs continuously and is often involved in the normal turnover and maturation of proteins. The cleavage event is catalyzed by specific proteases known as sheddases, which are often transmembrane proteins with a catalytic domain exposed to the extracellular space. These sheddases can be classified into different families, including the ADAM (a disintegrin and metalloprotease) family, the matrix metalloproteinase (MMP) family, and the furin family. The sheddases recognize specific cleavage sites within the ectodomain of their target proteins. These sites are often characterized by a specific amino acid sequence that is recognized by the active site of the protease. Following cleavage, the ectodomain is released from the cell surface and can undergo various fates, including:

* **Soluble signaling molecule:** Cleaved ectodomains can function as soluble signaling molecules, interacting with receptors on neighboring cells or distant tissues. This is a common mechanism for the regulation of cell-cell communication and the control of cellular processes.
* **Matrix remodeling:** Some ectodomains are involved in the extracellular matrix (ECM) and play a role in cell adhesion, migration, and tissue development. Their cleavage can modify the ECM, facilitating cell movement and tissue remodeling.
* **Regulation of protein function:** Cleavage can alter the activity or stability of the target protein. In some cases, the cleaved ectodomain may act as an antagonist of the intact protein, inhibiting its function.
* **Protein degradation:** Cleaved ectodomains can be degraded by extracellular proteases, contributing to protein turnover and maintaining cellular homeostasis.

The process of constitutive ectodomain proteolysis is tightly regulated to ensure proper cell function. Factors that influence sheddase activity include:

* **Cellular signaling pathways:** Specific signaling pathways can activate or inhibit sheddases, controlling the rate of ectodomain cleavage.
* **Post-translational modifications:** Sheddases can be regulated by post-translational modifications, such as phosphorylation or glycosylation, which can affect their activity or localization.
* **Expression levels of sheddases:** The levels of sheddases can be regulated by gene expression, influencing the overall rate of ectodomain cleavage.

Dysregulation of constitutive ectodomain proteolysis has been implicated in various diseases, including cancer, inflammation, and neurodegenerative disorders. Aberrant sheddase activity can lead to the inappropriate cleavage of target proteins, disrupting cellular processes and contributing to disease pathology.'
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Proteins (1)

Compounds (4)