Phase separation and a novel anti-cancer compound ACA-28 as regulators of PKC/MAPK signaling dynamics

Dear All,

Cell Signal Unit (Yamamoto Unit) would like to inform you of a seminar by Dr. Reiko Sugiura from Kindai University.

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Date: Wednesday, April 14, 2021

Time: 10:00-11:00

Venue: L4F01 (Lab 4, Level F) or

             ZOOM: https://oist.zoom.us/j/98995270828?pwd=NFgvdTdoSjc4RC9RZ05TbU91eHl0dz09

             Meeting ID: 989 9527 0828

             **If you need the passcode, please send e-mail to "yuki.nakagawa[at]oist.jp".

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Speaker:

Dr. Reiko Sugiura, Kindai University

Title:
Phase separation and a novel anti-cancer compound ACA-28 as regulators of PKC/MAPK signaling dynamics

Abstract:
  Mitogen-activated protein kinases (MAPKs), found in all eukaryotes, are signal-transducing enzymes playing a central role in a variety of biological processes, such as cell proliferation, survival, and differentiation.  Aberrant regulation of MAPK cascades contributes to cancer and other human diseases, thus posing the ERK MAPK pathway as a promising target for therapeutic intervention in cancer. 

  This study builds on our previous works on the discovery and intensive research efforts on the regulatory mechanisms of the MAPK signaling pathway in fission yeast.  We have developed molecular and chemical genetic screen based on the functional interaction between MAPK and calcineurin, which efficiently identified regulators and compounds modulating MAPK signaling in fission yeast and mammals. 

  In the first part of my talk, I will introduce our recent discovery that stress granules (SGs), non-membranous organelles composed of ribonucleoproteins (RNPs), play a key role in the spatiotemporal regulation of MAPK signaling by sequestrating Pck2/PKC, an upstream regulator of MAPK signaling.  Intriguingly, this finding led to the hypothesis that SG serves as a safeguard to protect against excessive MAPK signaling activation and cell death.

  In the second half of my talk, I will introduce an anti-cancer compound ACA-28 identified in our chemical genetic screen for modulators of ERK MAPK signaling. This compound has a unique feature to induce ERK-dependent apoptosis in several ERK active cancer cell lines including melanoma.  We also showed that ACA-28 downregulates DUSP6, a major phosphatase for ERK MAPK, thereby inducing cancer-specific apoptosis. Our findings thus provide novel and innovative cancer therapeutics to stimulate oncogenic signaling.

Host:
Prof. Tadashi Yamamoto

We hope to see many of you at the seminar.

Best regards,

Yuki Nakagawa

Research Unit Administrator

Cell Signal Unit