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"Likewise, cystine deprivation increases the SLC7A11 and USP18 interaction and enhances SLC7A11 deubiquitylation by USP18, whereas decreases the SLC7A11 and KCTD10 interaction and reduces SLC7A11 polyubiquitylation by KCTD10."

"Specifically, USP18 binds to again the cytoplasmic N-terminal domain of SLC7A11 via its internal domain (AA 51–150) and stabilizes SLC7A11 by extending its protein half-life (Zhou et al., 2024)."

"Likewise, cystine deprivation increases the SLC7A11 and USP18 interaction and enhances SLC7A11 deubiquitylation by USP18, whereas decreases the SLC7A11 and KCTD10 interaction and reduces SLC7A11 polyubiquitylation by KCTD10."

"Thus, we focused on USP18 for further detailed characterization.We first validated the interaction between SLC7A11 and USP18, and found that ectopically expressed SLC7A11 interacts with endogenous USP18 (Fig. 4B)."

"Moreover, the interaction between SLC7A11 and USP18 at endogenous levels was also detected (Fig. 4C)."

"Inactivation of CRL E3 ligase through neddylation blockage (by MLN4924) would, therefore, cause the accumulation of SLC7A11 at the transcriptional levels by the Keap1-NRF2-SLC7A11 and β-TrCP-ATF4-SLC7A11 axes through increased transcription, and at the posttranslational level by the KCTD10–SLC7A11 axis through reduced degradation.In this study, we also characterized USP18 as a deubiquitylase that stabilizes SLC7A11 with the following lines of supporting evidence: 1) USP18 binds to SLC7A11 through its intermediate domain (AA 51-150) and SLC7A11 interacts with USP18 through its N-terminal domain; 2) USP18 overexpression or knockdown increases or decreases SLC7A11 levels, by extending or shortening the SLC7A11 protein half-life, respectively; 3) USP18 decreases the levels of SLC7A11 polyubiquitylation.Whether or under what physiological and pathological conditions that SLC7A11 is subjected to KCTD10 and USP18 regulation?"

"We first validated the interaction between SLC7A11 and USP18, and found that ectopically expressed SLC7A11 interacts with endogenous USP18 ( xref )."

"In this study, we also characterized USP18 as a deubiquitylase that stabilizes SLC7A11 with the following lines of supporting evidence: 1) USP18 binds to SLC7A11 through its intermediate domain (AA 51-150) and SLC7A11 interacts with USP18 through its N-terminal domain; 2) USP18 overexpression or knockdown increases or decreases SLC7A11 levels, by extending or shortening the SLC7A11 protein half-life, respectively; 3) USP18 decreases the levels of SLC7A11 polyubiquitylation."

"Moreover, the interaction between SLC7A11 and USP18 at endogenous levels was also detected ( xref )."

"Here we showed a dynamic regulation of the SLC7A11 stability by KCTD10 and USP18 in response to cystine levels in the culture, as evidenced by 1) cystine deprivation decreases the levels of KCTD10, but increases the levels of USP18, which is reversed/rescued by cystine resupply, and 2) cystine deprivations disrupts the SLC7A11–KCTD10 interaction to reduce SLC7A11 ubiquitylation, whereas increases the SLC7A11–USP18 interaction to enhance SLC7A11 deubiquitylation."

"On the other hand, cystine deprivation enhanced the SLC7A11–USP18 interaction ( xref and), and promoted SLC7A11 deubiquitylation induced by USP18 ( xref )."