Fig. 5: HBS1L is a synthetic lethal target in cancers with SKIc loss.
From: Synthetic lethality of mRNA quality control complexes in cancer
a, HBS1L knockout in a panel of cell lines. Relative viability of sgHBS1L or sgB2M cells at day 7. Data are mean ± s.e.m. of n = 3 independent biological replicates. b, Model of the PELO–HBS1L complex, adapted from Protein Data Bank ID 5LZZ. PELO is shown in blue, HBS1L is in grey. Key HBS1L residues (568–682) along the PELO interaction surface are shown in salmon. GTPase catalytic residues T325 and H348 are circled with green and pink dotted lines, respectively. c, Validation of a stable NCI-H1299 sgHBS1L model (HBS1L KO) and HBS1L rescue constructs. d, Functional characterization of HBS1L. Data shown from n = 3 independent biological replicates. EV, empty vector, P = 1.7 × 10−5; wild type, P = 0.21; Δ1–140, P = 0.13; H348A, P = 6.6 × 10−5; T325A, P = 4.8 × 10−4; Δ568–682, P = 2.0 × 10−5. e, Co-immunoprecipitation of full-length HBS1L and HBS1L(Δ568–682) and PELO. Representative image of a single experiment from two independent biological replicates. f, Immunoblot for validation of the inducible sgHBS1L model. Experiment performed once. g, In vivo HBS1L dependency. Growth of size-matched (200 mm3) implanted doxycycline-inducible sgHBS1L MIAPACA2 model. Doxycycline (625 mg kg−1) chow was administered ad libitum. Data show mean ± s.e.m. of n  =  8 mice per group. P value calculated at study end, P = 3.9 × 10−4. Two-tailed Student’s t-test (a,d,g).
