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Ubiquitin‐ligase AIP 4 controls differential ubiquitination and stability of isoforms of the scaffold protein ITSN 1
Author(s) -
Dergai Oleksandr,
Dergai Mykola,
Rynditch Alla
Publication year - 2018
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 - 10.1002/1873-3468.13118
Subject(s) - ubiquitin , ubiquitin ligase , gene isoform , endocytic cycle , microbiology and biotechnology , chemistry , scaffold protein , f box protein , biochemistry , biology , signal transduction , endocytosis , gene , cell
At present, the role of ubiquitination of cargoes internalized from the plasma membrane is better understood than the consequences of ubiquitination of proteins comprising the endocytic machinery. Here, we show that the E3 ubiquitin ligase AIP 4/ ITCH contributes to the differential ubiquitination of isoforms of the endocytic scaffold protein intersectin1 ( ITSN 1). The major isoform ITSN 1‐s is monoubiquitinated, whereas the minor one, ITSN 1‐22a undergoes a combination of mono‐ and oligoubiquitination. The monoubiquitination is required for ITSN 1‐s stability, whereas the oligoubiquitination of ITSN 1‐22a causes its proteasomal degradation. This explains the observed low abundance of the minor isoform in cells. Thus, different modes of ubiquitination regulated by AIP 4 have opposite effects on ITSN 1 isoform stability.