Related Experiment Video
Updated: Dec 12, 2025
08:17
A High-Throughput Enzyme-Coupled Activity Assay to Probe Small Molecule Interaction with the dNTPase SAMHD1
Published on: April 16, 2021
2.7K
ITSN1 regulates SAM68 solubility through SH3 domain interactions with SAM68 proline-rich motifs
S Pankivskyi1,2, D Pastré1, E Steiner1
1SABNP, Univ Evry, INSERM U1204, Université Paris-Saclay, 91025, Evry, France.
Cellular and Molecular Life Sciences : CMLS
|August 12, 2020
Summary
Intersectin 1 (ITSN1) interaction with SAM68 protein enhances SAM68 solubility and disrupts nuclear bodies. This chaperoning mechanism may regulate mRNA processing, impacting neuronal functions and cancer.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- SAM68 is an mRNA-binding protein forming nuclear bodies (SNBs) crucial for mRNA processing.
- SAM68 is poorly soluble in vitro, posing challenges for studying its function.
Purpose of the Study:
- To investigate the interaction between SAM68 and intersectin 1 (ITSN1).
- To elucidate the role of ITSN1 in SAM68 solubility and nuclear body dynamics.
- To understand the potential impact on mRNA processing and cellular functions.
Main Methods:
- In vitro solubility assays.
- Cellular localization studies in HeLa cells.
- Analysis of protein-protein interactions using SH3 domains and proline-rich motifs (PRMs).
Main Results:
- ITSN1 enhances SAM68 solubility through its SH3 domains interacting with SAM68's PRMs.
- Specific ITSN1 SH3 domains (SH3A and SH3D) mediate these interactions.
- ITSN1 binding, along with mRNA, promotes SAM68 solubilization and induces SNB dissociation.
Conclusions:
- ITSN1 acts as a specific chaperone for PRM-rich SAM68 within nuclear ribonucleoprotein complexes.
- This interaction regulates mRNA processing, including SAM68-controlled splicing events.
- The findings provide a model for interactions between proline-rich RNA-binding proteins and SH3 domain-containing proteins.
Related Concept Videos
01:45Regulation of Nuclear Protein Sorting
3.1K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
3.1K
01:30Assembly of Signaling Complexes
6.3K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
6.3K
01:20The JAK-STAT Signaling Pathway
11.3K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
11.3K
02:26Conservation of Protein Domains Over Different Proteins
13.8K
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
13.8K
02:04Covalently Linked Protein Regulators
8.4K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
8.4K
01:45Tail-anchoring of Proteins in the ER Membrane
3.6K
Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
3.6K