Ubiquitin-independent proteasomal degradation of Spindlin-1 by the E3 ligase HACE1 contributes to cell-cell adhesion

Palicharla, Vivek Reddy; Gupta, Devanshi; Bhattacharya, Debjani und Maddika, Subbareddy (2021): Ubiquitin-independent proteasomal degradation of Spindlin-1 by the E3 ligase HACE1 contributes to cell-cell adhesion. In: Febs Letters, Vol. 595, No. 4: pp. 491-506

Abstract

HECT-E3 ligases play an essential role in catalyzing the transfer of ubiquitin to protein substrates. The noncatalytic roles of HECT-E3 ligases in cells are unknown. Here, we report that a HECT-E3 ligase, HACE1, functions as an adaptor independent of its E3 ligase activity. We identified Spindlin-1, a histone reader, as a new HACE1-associated protein. Interestingly, we found that HACE1 promotes Spindlin-1 degradation via the proteasome in an ubiquitination-independent manner. Functionally, we demonstrated that the loss of HACE1 results in weak cell-cell adhesion due to Spindlin-1-mediated accumulation of GDNF, a negative regulator of cell adhesion. Together, our data suggest that HACE1 acts as a molecular adaptor and plays an important noncatalytic role in presenting selected substrates directly to the proteasome for degradation.

• Item Type: Journal article
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 0014-5793
• Language: English