Related Experiment Video
Updated: Jan 3, 2026
08:36
Prostate Organoid Cultures as Tools to Translate Genotypes and Mutational Profiles to Pharmacological Responses
Published on: October 24, 2019
11.6K
SUMO3 modification by PIAS1 modulates androgen receptor cellular distribution and stability
Nanyang Yang1,2, Sitong Liu1,3, Tian Qin1
1The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, Northeast Normal University, 5268 People's Street, Changchun, Jilin, 130024, People's Republic of China.
Cell Communication and Signaling : CCS
|November 23, 2019
Summary
SUMO E3 ligase PIAS1 and SUMO3 modify androgen receptor (AR) signaling by promoting AR cytosolic translocation and degradation. This crosstalk between AR sumoylation and ubiquitination is crucial for regulating AR stability in prostate cancer.
Area of Science:
- Molecular Biology
- Cancer Research
- Cellular Signaling
Background:
- Reactivation of androgen receptor (AR) signaling drives castration-resistant prostate cancer (CRPC).
- AR overexpression and down-regulation contribute to CRPC progression.
- The role of SUMO E3 ligases, like PIASs, in regulating AR sumoylation, distribution, and stability remains unclear.
Purpose of the Study:
- To investigate the effect of SUMO3 modification on AR intracellular localization and degradation.
- To characterize AR sumoylation sites and key PIAS1 residues involved in AR regulation.
- To elucidate the interaction between PIAS1, SUMO3, and MDM2 in AR degradation.
Main Methods:
- Immunostaining in AR-negative prostate cancer DU145 cells to assess AR localization.
- Overexpression of PIAS1 and SUMO3 to study AR sumoylation and degradation.
- Characterization of sumoylation sites on AR and PIAS1, and their interaction with MDM2.
Main Results:
- PIAS1 and SUMO3 mediate AR cytosolic translocation and degradation via the ubiquitin-proteasome pathway.
- AR sumoylation precedes ubiquitination, with specific lysine residues (AR K386, K845) critical for PIAS1/SUMO3-induced degradation.
- Sumoylated PIAS1 interacts with AR and recruits MDM2 for AR ubiquitination and degradation.
Conclusions:
- SUMO3 modification of PIAS1 regulates AR cellular distribution and stability.
- This study reveals a crosstalk between AR sumoylation and ubiquitination mediated by PIAS1 and SUMO3.
- Findings provide insights into AR regulation mechanisms in prostate cancer.
Related Concept Videos
02:23Abnormal Proliferation
5.0K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.0K
01:22PI3K/mTOR/AKT Signaling Pathway
5.2K
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...
5.2K
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
02:04Covalently Linked Protein Regulators
8.6K
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....
8.6K
01:20The JAK-STAT Signaling Pathway
11.7K
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...
11.7K
01:23Regulation of Expression at Multiple Steps
1.3K
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
1.3K