Background: The HERC family contains six members from HERC1 to HERC6 that are featured with
the HECT domains that exerts ubiquitin ligase activity and the RCC1-like domains that are involved in cell cycle
regulation. Although identified as early as 1990s, their biological functions are extensively studied in recent
years. More and more researches have demonstrated that the HERC ubiquitin ligases are widely engaged in carcinogenesis,
however, there lacks a comprehensive and instructive analysis.
Methods: The PubMed database was searched by keywords of individual HERC proteins (such as HERC4) and
cancer. The emerging roles of HERC proteins in cancer and the specific mechanisms were collectively analyzed
Results: HERC proteins belong to the HECT domain-containing ubiquitin ligases that can identify and mediate
the ubiquitination of specific substrate proteins. All HERC ubiquitin ligases except HERC6 have been assigned
one or more than one ubiquitination substrates. In all of HERCs, HERC1 and HERC2 have been widely studied,
in contrast, there are no reported studies yet on protein ubiquitination mediated by HERC6. Dependent on the
protein substrates, HERC proteins may act as a tumor suppressor or oncoprotein in specific cancer types. For
example, HERC4 is believed to contribute to carcinogenesis of solid tumors such as lung cancer, but it suppresses
the proliferation of myeloma cells.
Conclusion: HERC proteins as ubiquitin ligases are widely involved in various cancers. Targeting at specific
HERC proteins could be a strategy for the treatment of certain cancers.