The NSD family of protein methyltransferases in human cancer

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• The NSD (Nuclear Set Domain) family comprises protein lysine methyltransferases NSD1, NSD2, and NSD3.
• Dysfunction of NSD proteins is linked to developmental disorders like Wolf-Hirschhorn and Sotos syndromes.
• Emerging evidence implicates NSD family members in various cancers.

Purpose of the Study:

• To review the current understanding of NSD protein roles in cancer.
• To highlight the involvement of NSD methyltransferases in oncogenesis.
• To explore the therapeutic potential of targeting NSD proteins in cancer treatment.

Main Methods:

• Literature review of studies on NSD proteins and cancer.
• Analysis of research on NSD protein expression, mutation, and amplification in tumors.
• Examination of NSD protein functions in epigenomic regulation and nonhistone modification.

Main Results:

• NSD methyltransferases are frequently overexpressed, amplified, or mutated in diverse cancer types.
• Dysregulation of NSD enzymes leads to epigenomic aberrations driving oncogenesis.
• NSD1 methylates the nonhistone protein RELA/p65, suggesting roles beyond histone modification.

Conclusions:

• NSD family proteins play a significant role in cancer development and progression.
• The involvement of NSD proteins in both histone and nonhistone methylation pathways is critical.
• Targeting NSD methyltransferases represents a potential strategy for developing new cancer therapies.