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Treating diseases at their origin

Date:
June 17, 2016
Source:
Hokkaido University
Summary:
Scientists are getting closer to understanding the function of a protein involved in vital cellular processes. This may lead to the discovery of drugs that can treat some cancers and autoimmune disorders.
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Signaling cascade for STAT3 activation. ARL3 binds to STAT3, facilitating its transportation and accumulation in the nucleus. JAKs induce the tyrosine phosphorylation of STAT3. The phosphorylated STAT3 forms a dimer and translocates from the cytoplasm to the nucleus where it binds to DNA and coactivators and induces gene transcription.
Credit: Hokkaido University

Hokkaido University scientists are getting closer to understanding the function of a protein involved in vital cellular processes. This may lead to the discovery of drugs that can treat some cancers and autoimmune disorders.

The protein STAT3 plays an important role in cell proliferation, survival and migration, making it an important modulator in inflammatory and malignant diseases. Mutations to the gene that signals its production can lead to a variety of diseases, including cancers and autoimmune disorders such as lymphoma, leukemia, and childhood-onset autoimmunity. Understanding how STAT3 works is important to finding drugs that can treat these diseases.

Scientists at Hokkaido University in Japan investigated the molecular mechanisms that regulate STAT3 activity. They found that another protein, called ARL3, played an important role in the STAT3 pathway. By recognizing and strongly binding to STAT3, it facilitates the transportation of STAT3 into the nucleus and its accumulation there. In the nucleus, STAT3 then binds to special DNA sequences to regulate the turning on and off of certain genes.

Inhibiting the expression of ARL3 in cultured cells led to a decrease in STAT3's activity and consequently in the expression of its target genes. It also supressed STAT3-dependent proliferation of cells, indicating ARL3's important regulatory role on STAT3 and its pathways.

Based on previous studies, the team believes that ARL3 might also influence certain proteins involved in the transfer of STAT3 and other molecules into and out of the nucleus. Additionally, they believe that ARL3 might regulate STAT3 by facilitating its interaction with microtubules, which help to transport substances within the cell.

"Clarifying each step of STAT3 regulation is important because STAT3 is a key player in the pathogenesis of diverse human diseases and is a prime target for novel therapies," the researchers write in their study, published in the Journal of Biological Chemistry. "Specific inhibitors of the STAT3-ARL3 pathway are good candidates for the treatment of STAT3-related human diseases."


Story Source:

Materials provided by Hokkaido University. Note: Content may be edited for style and length.


Journal Reference:

  1. Sumihito Togi, Ryuta Muromoto, Koki Hirashima, Yuichi Kitai, Taichiro Okayama, Osamu Ikeda, Naoki Matsumoto, Shigeyuki Kon, Yuichi Sekine, Kenji Oritani, Tadashi Matsuda. A New STAT3-binding Partner, ARL3, Enhances the Phosphorylation and Nuclear Accumulation of STAT3. Journal of Biological Chemistry, 2016; 291 (21): 11161 DOI: 10.1074/jbc.M116.724849

Cite This Page:

Hokkaido University. "Treating diseases at their origin." ScienceDaily. ScienceDaily, 17 June 2016. <www.sciencedaily.com/releases/2016/06/160617113852.htm>.
Hokkaido University. (2016, June 17). Treating diseases at their origin. ScienceDaily. Retrieved May 23, 2017 from www.sciencedaily.com/releases/2016/06/160617113852.htm
Hokkaido University. "Treating diseases at their origin." ScienceDaily. www.sciencedaily.com/releases/2016/06/160617113852.htm (accessed May 23, 2017).

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