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Ubiquitin‐independent proteasomal degradation of Spindlin‐1 by the E3 ligase HACE1 contributes to cell–cell adhesion
Author(s) -
Palicharla Vivek Reddy,
Gupta Devanshi,
Bhattacharya Debjani,
Maddika Subbareddy
Publication year - 2021
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.14031
Subject(s) - ubiquitin ligase , ubiquitin , microbiology and biotechnology , proteasome , signal transducing adaptor protein , chemistry , dna ligase , cell adhesion , biochemistry , cell , biology , signal transduction , enzyme , gene
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.