Related Experiment Video
Updated: May 1, 2026
14:08
Study of Protein-protein Interactions in Autophagy Research
Published on: September 9, 2017
8.5K
The TRIM-FLMN protein TRIM45 directly interacts with RACK1 and negatively regulates PKC-mediated signaling pathway
T Sato1, H Takahashi2, S Hatakeyama2
11] Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan [2] Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Oncogene
|April 1, 2014
Summary
Tripartite motif-containing 45 (TRIM45) interacts with RACK1 and downregulates the mitogen-activated protein kinase (MAPK) pathway. TRIM45 acts as a negative feedback mechanism in MAPK signaling, crucial for controlling cell growth.
Area of Science:
- Molecular Biology
- Cell Signaling
- Cancer Research
Background:
- Receptor for activated C-kinase 1 (RACK1) is a scaffolding protein involved in protein kinase C (PKC) signaling.
- RACK1 plays a role in tumorigenesis and constitutive activation of MAPK-ERK signaling in melanoma.
- RACK1 is implicated in the mitogen-activated protein kinase (MAPK) signaling pathway.
Purpose of the Study:
- To identify novel RACK1-interacting proteins.
- To investigate the role of TRIM45 in MAPK signal transduction.
- To elucidate the function of TRIM45 in the negative feedback regulation of the MAPK pathway.
Main Methods:
- Co-immunoprecipitation to identify RACK1-interacting proteins.
- Western blotting to assess protein expression and signaling pathway activation.
- Analysis of TRIM45 expression in response to MAPK pathway activation.
Main Results:
- TRIM45 was identified as a novel RACK1-interacting protein.
- TRIM45 was found to downregulate MAPK signal transduction.
- TRIM45 expression is induced by extracellular stimuli that activate the MAPK pathway, leading to pathway attenuation.
Conclusions:
- TRIM45 negatively regulates MAPK signaling.
- TRIM45 acts as a negative feedback component in the MAPK pathway.
- TRIM45 may play a role in controlling cell growth and proliferation by modulating MAPK signaling.
Related Concept Videos
01:22PI3K/mTOR/AKT Signaling Pathway
5.1K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
5.1K
01:20The JAK-STAT Signaling Pathway
10.2K
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...
10.2K
01:07MAPK Signaling Cascades
7.3K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
7.3K
01:22Amplifying Signals via Enzymatic Cascade
15.3K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
15.3K
01:00Enzyme-linked Receptors
64.6K
Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
64.6K
01:19Interactions Between Signaling Pathways
4.7K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
4.7K