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In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
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E3 ligases and deubiquitinating enzymes regulating the MAPK signaling pathway in cancers

Hong-Beom Park1, Kwang-Hyun Baek1

  • 1Department of Biomedical Science, CHA University, Gyeonggi-Do 13488, Republic of Korea.

Biochimica Et Biophysica Acta. Reviews on Cancer
|May 19, 2022
PubMed

Insights

Mitogen-activated protein kinase (MAPK) pathways regulate cell functions and are implicated in cancer. This review details how E3 ligases and deubiquitinating enzymes (DUBs) modify MAPK signaling components in cancer.

Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Oncology

Background:

  • The mitogen-activated protein kinase (MAPK) signaling pathway is crucial for regulating cellular processes like proliferation, differentiation, and stress responses.
  • MAPK pathways involve a cascade of three kinase types: MAPKKK, MAPKK, and MAPK, transmitting external signals to cellular outputs.
  • Ubiquitination, a post-translational modification, and deubiquitination, its removal by deubiquitinating enzymes (DUBs), dynamically regulate protein function.

Purpose of the Study:

  • To review the mechanisms of MAPK signaling pathways (ERK1/2, ERK5, p38, JNK1/2/3) in the context of cancer.
  • To summarize the roles of E3 ligases and DUBs that target key MAPK signaling components.

Main Methods:

  • Literature review focusing on MAPK signaling pathways in cancer.
  • Analysis of studies investigating E3 ligases and DUBs targeting MAPK pathway components.

Main Results:

  • MAPK pathways are frequently dysregulated in various cancers.
  • E3 ligases and DUBs play critical roles in modulating the activity and stability of MAPK signaling components, including Raf, MEK1/2, ERK1/2, MEKKs, TAK1, DLK1, MLK1-4, ASK1/2, and MKK3-7.
  • These modifications by E3 ligases and DUBs significantly impact cancer cell behavior.

Conclusions:

  • Understanding the interplay between MAPK signaling, E3 ligases, and DUBs is essential for cancer research.
  • Targeting these regulatory mechanisms offers potential therapeutic strategies for cancer treatment.
Keywords:
Cancer therapeuticsDeubiquitinationMitogen-activated protein kinaseUbiquitination

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