regulation of protein import into nucleus
Definition
Target type: biologicalprocess
Any process that modulates the frequency, rate or extent of movement of proteins from the cytoplasm to the nucleus. [GOC:jl]
The regulation of protein import into the nucleus is a complex and tightly controlled process that ensures the proper localization and function of nuclear proteins. This process involves a series of steps, each of which is regulated by specific factors.
**1. Recognition and Binding:**
* Nuclear localization signals (NLS) are short amino acid sequences that are typically rich in basic residues (lysine and arginine). They are recognized and bound by nuclear import receptors (importins).
* Importins are a family of proteins that mediate the transport of proteins across the nuclear pore complex (NPC), a large protein channel that spans the nuclear envelope.
* Different importins recognize different NLS sequences, allowing for the selective transport of specific proteins.
**2. Translocation through the NPC:**
* The importin-cargo complex binds to the NPC and is translocated through the channel in a GTP-dependent manner.
* Ran, a small GTPase, plays a critical role in regulating this process.
* RanGTP binds to importins, causing them to release their cargo inside the nucleus.
**3. Release of Cargo:**
* Once inside the nucleus, RanGTP binds to importin, causing it to release the cargo protein.
* The importin-RanGTP complex then exits the nucleus via the NPC.
**4. Recycling of Importins:**
* Importins are recycled back to the cytoplasm, where they can bind to new cargo proteins.
* RanGAP, a GTPase-activating protein, converts RanGTP to RanGDP in the cytoplasm.
* RanGDP has a low affinity for importins and is unable to bind to cargo proteins.
**5. Regulation of Import:**
* The import process is tightly regulated by various factors, including:
* Concentration of RanGTP and RanGDP in the nucleus and cytoplasm
* Availability of importins
* Post-translational modifications of cargo proteins
* Signal transduction pathways
**6. Export of Proteins:**
* The export of proteins from the nucleus follows a similar mechanism to import, but with different proteins involved.
* Exportin proteins bind to nuclear export signals (NES) on cargo proteins and facilitate their translocation through the NPC in a RanGTP-dependent manner.
**7. Importance of Nuclear Import:**
* The regulation of nuclear import is essential for maintaining the integrity and function of the nucleus.
* Incorrect protein localization can lead to various cellular defects, including:
* Errors in gene expression and regulation
* Defects in DNA replication and repair
* Disruption of cellular signaling pathways
* Development of diseases'
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Proteins (1)
| Protein | Definition | Taxonomy |
|---|---|---|
| Bone morphogenetic protein 4 | A bone morphogenetic protein 4 that is encoded in the genome of human. [PRO:CNA, UniProtKB:P12644] | Homo sapiens (human) |
Compounds (3)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| dorsomorphin | dorsomorphin : A pyrazolopyrimidine that is pyrazolo[1,5-a]pyrimidine which is substituted at positions 3 and 6 by pyridin-4-yl and p-[2-(piperidin-1-yl)ethoxy]phenyl groups, respectively. It is a potent, selective, reversible, and ATP-competitive inhibitor of AMPK (AMP-activated protein kinase, EC 2.7.11.31) and a selective inhibitor of bone morphogenetic protein (BMP) signaling. dorsomorphin: an AMPK inhibitor | aromatic ether; piperidines; pyrazolopyrimidine; pyridines | bone morphogenetic protein receptor antagonist; EC 2.7.11.31 {[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase} inhibitor |
| ldn 193189 | LDN 193189: inhibits bone morphogenetic protein signaling | pyrimidines | |
| ml347 | ML347: an ALK2 inhibitor; structure in first source |