negative regulation of protein homodimerization activity

Definition

Target type: biologicalprocess

Any process that decreases the frequency, rate or extent of protein homodimerization, interacting selectively with an identical protein to form a homodimer. [GOC:dph, GOC:tb]

Negative regulation of protein homodimerization activity is a fundamental biological process that controls the formation and activity of protein complexes composed of two identical subunits. This regulation is crucial for maintaining cellular homeostasis, as uncontrolled dimerization can lead to aberrant signaling and disease.

Here's a detailed description of the process:

1. **Formation of Homodimers:** Two identical protein monomers, through interactions mediated by specific domains, associate to form a stable dimer. This process often involves non-covalent interactions, such as hydrophobic interactions, hydrogen bonds, and electrostatic interactions.

2. **Regulation of Dimerization:** Several mechanisms contribute to regulating homodimerization:

a. **Protein Modifications:** Post-translational modifications, such as phosphorylation, acetylation, or ubiquitination, can alter the conformation of a protein, influencing its ability to dimerize. These modifications can either promote or inhibit dimerization.

b. **Binding of Regulatory Molecules:** Ligands, including small molecules, peptides, or other proteins, can bind to specific sites on the protein, thereby modulating its dimerization potential. Some ligands can promote dimerization, while others can disrupt it.

c. **Subcellular Localization:** Segregation of proteins to different cellular compartments can limit their interaction and subsequent dimerization. For example, proteins residing in the nucleus may not be able to dimerize with proteins located in the cytoplasm.

d. **Protein Degradation:** Cellular degradation pathways, like the ubiquitin-proteasome system, can target and remove proteins that promote aberrant dimerization.

3. **Consequences of Regulated Dimerization:**

a. **Altered Signaling Pathways:** Homodimers often act as signaling molecules or transcription factors. Regulation of dimerization controls the strength and duration of signaling events.

b. **Control of Protein Activity:** Dimerization can modulate protein activity, either enhancing or inhibiting its function. This is particularly important in enzymes, where dimerization can influence substrate binding or catalytic activity.

c. **Disease Association:** Dysregulation of protein homodimerization is implicated in various diseases, including cancer, neurodegenerative disorders, and metabolic diseases.

4. **Examples of Regulation:**

a. **Transcription Factors:** Transcription factors often require dimerization for DNA binding and transcriptional regulation.

b. **Kinases:** Many protein kinases, such as cyclin-dependent kinases (CDKs), require dimerization for activation.

c. **Growth Factors:** Growth factors, such as epidermal growth factor (EGF), dimerize upon binding to their receptors, triggering downstream signaling pathways.

In summary, negative regulation of protein homodimerization is a complex process involving multiple molecular mechanisms. This regulation ensures appropriate formation of protein complexes and maintains cellular homeostasis, preventing aberrant signaling and disease.'
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Proteins (1)

Compounds (6)