The Physiological functions of IKK-selective substrate identification and their critical roles in diseases

Jian-shuai Yu; Jin Jin; Yi-yuan Li

doi:10.37175/stemedicine.v1i4.49

Jian-shuai Yu Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China.
Jin Jin MOE Laboratory of Biosystem Homeostasis and Protection, and Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.
Yi-yuan Li Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China.

DOI: https://doi.org/10.37175/stemedicine.v1i4.49

Keywords: NF-κB, IKKs, Substrates, Immune response, Disease

Abstract

The nuclear factor κB (NF-κB) transcription factors exert central hub functions in multiple physiological
processes including immune response, cell survival, proliferation and cytokine production, which has
naturally become the core of research almost in all aspects of biomedical science over 30 years. Since
both the activation and termination of NF-κB pathway are tightly regulated, little alteration can lead to
excessive inflammatory responses and even result in tissue damage and severe diseases. The inhibitor of
nuclear factor kappa-B (IκB) kinase (IKK) complex is the main regulator of the NF-κB signaling pathway,
they mediate and deliver signals through phosphorylating certain substrates. In recent years, increased
proteins have been identified to be targeted by IKK members and the particular modification mechanism
becomes clear with the development of detecting techniques and structural biology. In this review, we
summarize the known substrates of IKK family members either relevant or irrelevant to NF-κB signaling,
their structures and phosphorylation patterns, and the related physiologic and/or pathologic responses.
Understanding the regulation of IKKs on their substrates may be helpful to connect IKKs with specific
signaling pathways or physiological phenomena, and is essential for targeting IKKs in clinical research.

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