Protein lipidation in health and disease: molecular basis, physiological function and pathological implication

Area of Science:

• Biochemistry and Molecular Biology
• Cellular and Molecular Physiology

Background:

• Posttranslational modifications, including protein lipidations, enhance protein complexity and functional diversity.
• Protein lipidations, such as S-palmitoylation and N-myristoylation, are vital for regulating protein trafficking, stability, and signal transduction.
• Dysregulation of protein lipidation is linked to various diseases, highlighting its physiological significance.

Purpose of the Study:

• To comprehensively review regulatory enzymes and mechanisms of protein lipidation.
• To outline the impact of protein lipidations on physiology and disease.
• To highlight potential therapeutic targets and clinical research progress in targeting protein lipidations.

Main Methods:

• Review of existing genetic, structural, and biomedical studies.
• Analysis of regulatory enzymes and catalytic mechanisms for different lipidation types.
• Examination of preclinical and clinical research on drugs targeting protein lipidations.

Main Results:

• Protein lipidations are essential for protein localization, stability, and interactions, influencing broad physiological functions.
• Several drugs targeting protein lipidations, like asciminib and lonafarnib, have received FDA approval.
• Targeting protein lipidations presents a promising strategy for therapeutic intervention in various diseases.

Conclusions:

• Protein lipidation is a critical regulatory mechanism in cellular processes and disease pathogenesis.
• The development of drugs targeting protein lipidations demonstrates significant therapeutic potential.
• This review serves as a reference for future research into protein lipidation mechanisms and therapeutic applications.