Related Experiment Video
Updated: Mar 22, 2026
14:08
Study of Protein-protein Interactions in Autophagy Research
Published on: September 9, 2017
9.7K
Chaperone-like protein HYPK and its interacting partners augment autophagy
Kamalika Roy Choudhury1, Sudha Bucha1, Shounak Baksi1
1Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, 1/AF, Bidhan Nagar, Kolkata 700 064, India.
European Journal of Cell Biology
|April 13, 2016
Summary
Huntingtin-interacting protein HYPK promotes cellular autophagy, a process crucial for clearing toxic protein aggregates. Overexpressing HYPK enhances autophagy and helps clear mutant huntingtin, offering potential therapeutic insights for Huntington's disease.
Area of Science:
- Cellular Biology
- Neuroscience
- Molecular Biology
Background:
- Huntingtin-interacting protein (HYPK) has chaperone-like activity and interacts with huntingtin (HTT).
- Previous studies identified HYPK interacting partners suggesting roles in Huntington's disease (HD).
- The specific role of HYPK in cellular processes like autophagy remained unclear.
Purpose of the Study:
- To investigate the role of HYPK in autophagy.
- To determine if HYPK can influence the clearance of mutant huntingtin aggregates.
Main Methods:
- Co-immunoprecipitation and co-localization to identify HYPK interacting partners.
- Analysis of primary (54) and secondary (1026) HYPK interactors for autophagy association.
- Overexpression and knockdown of HYPK in mouse striatal cells (STHdh(Q7)/Hdh(Q7)).
- Assessment of autophagy markers (LC3I conversion, BECN1, ATG5-ATG12, Tfeb, Srebp2, Zkscan3) and mutant HTT levels.
Main Results:
- 10 primary and 91 secondary HYPK interactors are linked to autophagy.
- HYPK overexpression significantly increased cellular autophagy.
- HYPK knockdown decreased autophagy levels.
- HYPK overexpression restored autophagy markers reduced by N-terminal mutant HTT.
- HYPK appears to aid in clearing mutant HTT aggregates via autophagy.
Conclusions:
- HYPK is a key regulator that induces and enhances cellular autophagy.
- HYPK plays a significant role in the autophagic clearance of mutant huntingtin aggregates.
- HYPK represents a potential therapeutic target for managing Huntington's disease by modulating autophagy.
Related Concept Videos
03:00Molecular Chaperones and Protein Folding
20.7K
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
The...
20.7K
03:00Molecular Chaperones and Protein Folding
15.5K
15.5K
01:26Bacterial Protein Maturation
683
Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
683
01:27Autophagy
6.1K
Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
6.1K
01:36Delivery Pathways to the Lysosome
10.5K
Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
10.5K
01:32Export of Misfolded Proteins out of the ER
5.4K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
5.4K