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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)

ProteinDefinitionTaxonomy
Integrin alpha-4An integrin alpha-4 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P13612]Homo sapiens (human)

Compounds (6)

CompoundDefinitionClassesRoles
haloperidolhaloperidol : A compound composed of a central piperidine structure with hydroxy and p-chlorophenyl substituents at position 4 and an N-linked p-fluorobutyrophenone moiety.

Haloperidol: A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)
aromatic ketone;
hydroxypiperidine;
monochlorobenzenes;
organofluorine compound;
tertiary alcohol
antidyskinesia agent;
antiemetic;
dopaminergic antagonist;
first generation antipsychotic;
serotonergic antagonist
1,3-ditolylguanidine1,3-ditolylguanidine: structure given in first source; a selective ligand for the sigma binding sites in the braintoluenes
cyclopaminepiperidinesglioma-associated oncogene inhibitor
mocetinostatmocetinostat : A benzamide obtained by formal condensation of the carboxy group of 4-({[4-(pyridin-3-yl)pyrimidin-2-yl]amino}methyl)benzoic acid with one of the amino groups of benzene-1,2-diamine. It is an orally active and isotype-selective HDAC inhibitor which exhibits antitumour activity (IC50 = 0.15, 0.29, 1.66 and 0.59 muM for HDAC1, HDAC2, HDAC3 and HDAC11).

mocetinostat: undergoing phase II clinical trials for treatment of cancer
aminopyrimidine;
benzamides;
pyridines;
secondary amino compound;
secondary carboxamide;
substituted aniline
antineoplastic agent;
apoptosis inducer;
autophagy inducer;
cardioprotective agent;
EC 3.5.1.98 (histone deacetylase) inhibitor;
hepatotoxic agent
tr 14035N-(2,6-dichlorobenzoyl)-4-(2',6'-bismethoxyphenyl)phenylalanine: TR-14035 is the (L)-isomer; an antagonist of both alpha4beta1 and beta7 integrins; structure in first source
bio 1211BIO 1211: integrin alpha4beta1 inhibitor; structure in first source