K48

K48 refers primarily to a type of polyubiquitin chain in eukaryotic cells, formed when ubiquitin molecules are linked through lysine-48 on ubiquitin. In the ubiquitination cascade, an E1 activating enzyme transfers ubiquitin to an E2 conjugating enzyme, and an E3 ligase facilitates the attachment of ubiquitin to substrates or to another ubiquitin, enabling chain growth.

K48-linked chains signal for proteasomal degradation. The 26S proteasome recognizes Lys-48 linked polyubiquitin and degrades the tagged substrate, often after unfolding. The length and topology of the chain can influence degradation efficiency, with longer K48 chains generally promoting robust degradation. Deubiquitinating enzymes may remove or trim K48 chains, rescuing substrates or adjusting degradation timing.

In cells, K48-mediated proteolysis participates in regulating processes such as cell cycle progression, DNA damage response, and stress signaling. Dysregulation of K48 chain formation or removal is associated with diseases, including cancer and neurodegenerative disorders. Because K48 signaling governs protein turnover, it remains a focus of research and therapeutic interest, including the development of proteasome inhibitors and strategies that modulate ubiquitin pathway enzymes.