Biological functions of hyaluronan and cytokine-inducible deubiquitinating enzymes

• Importance of hyaluronan and its role in cancer progression.
• Deubiquitinating enzymes (DUBs) encoding hyaluronan binding motifs induce apoptosis.
• Mapping hyaluronan binding motifs (HABMs) in DUBs which promote apoptosis
• First attempt to show the relationship between DUBs and hyaluronan
• Suggesting DUBs with HABMs as potential anticancer therapeutics

The modification of proteins through post-translation and degradation by the ubiquitin–proteasome system plays a pivotal role in a broad array of biological processes. Reversal of this process by deubiquitination is a central step in the maintenance and regulation of cellular homeostasis. It now appears that the regulation of ubiquitin pathways by deubiquitinating enzymes (DUBs) could be used as targets for anticancer therapy. Recent success in inducing apoptosis in cancerous cells by USP17, a cytokine-inducible DUB encoding two hyaluronan binding motifs (HABMs) showing direct interaction with hyaluronan (HA), could prove a promising step in the development of DUBs containing HABMs as agents in anticancer therapeutics. In this review, we summarize the importance of hyaluronan (HA) in cancer, the role played by DUBs in apoptosis, and a possible relationship between DUBs and HA in cancerous cells, suggesting new strategies for applying DUB enzymes as potential anticancer therapeutics.