cytokine precursor processing

Definition

Target type: biologicalprocess

The cleavage of a peptide bond in a precursor form of a cytokine, resulting in the mature (active) form of the cytokine. [PMID:29247995]

Cytokine precursor processing is a crucial step in the regulation of immune responses. It involves the conversion of inactive precursor forms of cytokines, synthesized as pro-cytokines, into their biologically active forms. This intricate process is orchestrated by a series of enzymatic events, primarily proteolytic cleavage, which are tightly regulated to ensure proper cytokine function and prevent excessive inflammation.

The pro-cytokine precursor, typically synthesized as a single polypeptide chain, contains a signal peptide at the N-terminus and a mature cytokine domain. The signal peptide guides the pro-cytokine to the endoplasmic reticulum (ER), where it undergoes folding and quality control. Once properly folded, the pro-cytokine is transported to the Golgi apparatus.

Within the Golgi, pro-cytokines undergo post-translational modifications, including glycosylation and phosphorylation. These modifications can influence their stability, activity, and receptor binding. Crucially, proteolytic cleavage, mediated by specific proteases, removes the N-terminal pro-peptide, revealing the active cytokine domain.

The proteases responsible for pro-cytokine processing are often highly specific, ensuring targeted activation of individual cytokines. For instance, furin, a proprotein convertase, plays a key role in processing pro-TNFα and pro-IL-1β. Other proteases, such as caspase-1, are involved in the processing of specific pro-inflammatory cytokines, such as IL-1β and IL-18.

Cytokine precursor processing is tightly regulated to prevent uncontrolled inflammation. Cells express specific inhibitors, such as serpins, that can bind to and inhibit the activity of pro-converting enzymes. This regulation ensures that cytokine activation occurs only when necessary, preventing excessive immune responses that can lead to tissue damage.

Furthermore, some pro-cytokines are stored as inactive precursors within specialized secretory vesicles, such as lysosomes or granules. These vesicles provide a mechanism for rapid release of active cytokines in response to specific stimuli, such as bacterial infection or inflammation.

In summary, cytokine precursor processing is a complex and precisely regulated process that involves several enzymatic events, primarily proteolytic cleavage. It ensures the appropriate timing and localization of cytokine activation, preventing uncontrolled inflammation and facilitating a balanced immune response.'
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Proteins (3)

Compounds (57)