Figure 6.

USP9X-mediated regulation of RIT1 is relevant across cancer types

(A) Correlation of proteomics data⁵⁰ from the Cancer Dependency Map (DepMap) comparing USP9X (Q93008) and RIT1 (Q92963-3). Pearson r and p values calculated in Prism. Pink dots indicate non-small cell lung cancer cell lines.

(B) Correlation of DepMap proteomics data⁵⁰ comparing USP9X (Q93008) and CDC20 (Q12834). Pearson r and p values calculated in Prism. Pink dots indicate non-small cell lung cancer cell lines.

(C) Correlation of DepMap mRNA expression data (Expression Public 23Q2)⁵¹ for RIT1 and USP9X proteomics data (Q93008).⁵⁰ Pearson r and p values calculated in Prism. Pink dots indicate non-small cell lung cancer cell lines.

(D) Correlation of DepMap mRNA expression data (Expression Public 23Q2)⁵¹ for CDC20 and USP9X proteomics data (Q93008).⁵⁰ Pearson r and p values calculated in Prism. Pink dots indicate non-small cell lung cancer cell lines.

(E) Proposed model (left) of RIT1 protein regulation. RIT1^WT is ubiquitinated by LZTR1, while RIT1^M90I is ubiquitinated by a currently unknown E3 ligase. USP9X counteracts the ubiquitination of both wild-type and mutant RIT1. Increased RIT1 abundance and stability are important for RIT1 function and disease progression. The exact biological consequences of RIT1^WT amplification have yet to be elucidated. Genetic knockout (right) of USP9X prevents RIT1 deubiquitination, thereby promoting RIT1 degradation and abrogating oncogenic phenotypes. Figure created with BioRender.com.

See also Figure S5.