biostudies-literatureShaw TINCI NIH HHSNIHNIGMS NIH HHS5154https://www.ebi.ac.uk/biostudies/studies/S-EPMC7933146biostudies-literatureUnknown11(1)USP7, which encodes a deubiquitylating enzyme, is among the most frequently mutated genes in pediatric T-ALL, with somatic heterozygous loss-of-function mutations (haploinsufficiency) predominantly affecting the subgroup that has aberrant TAL1 oncogene activation. Network analysis of > 200 T-ALL transcriptomes linked USP7 haploinsufficiency with decreased activities of E-proteins. E-proteins are also negatively regulated by TAL1, leading to concerted down-regulation of E-protein target genes involved in T-cell development. In T-ALL cell lines, we showed the physical interaction of USP7 with E-proteins and TAL1 by mass spectrometry and ChIP-seq. Haploinsufficient but not complete CRISPR knock-out of USP7 showed accelerated cell growth and validated transcriptional down-regulation of E-proteScientific reportsIntegrative network analysis reveals USP7 haploinsufficiency inhibits E-protein activity in pediatric T-lineage acute lymphoblastic leukemia (T-ALL).PMC7933146R01 GM134382R01 CA2163911R01CA216391-01A1R35 CA210064Shaw TICheng CTian LLook ATQian CKavdia KZhang JPagala VREaston JGu WMa XDong LChoi JPorter SNYu JJu BPei DLiu YPruett-Miller SMHigh AJanke LJDowning JRShaner BPeng JfalseIntegrative network analysis reveals USP7 haploinsufficiency inhibits E-protein activity in pediatric T-lineage acute lymphoblastic leukemia (T-ALL).USP7, which encodes a deubiquitylating enzyme, is among the most frequently mutated genes in pediatric T-ALL, with somatic heterozygous loss-of-function mutations (haploinsufficiency) predominantly affecting the subgroup that has aberrant TAL1 oncogene activation. Network analysis of > 200 T-ALL transcriptomes linked USP7 haploinsufficiency with decreased activities of E-proteins. E-proteins are also negatively regulated by TAL1, leading to concerted down-regulation of E-protein target genes involved in T-cell development. In T-ALL cell lines, we showed the physical interaction of USP7 with E-proteins and TAL1 by mass spectrometry and ChIP-seq. Haploinsufficient but not complete CRISPR knock-out of USP7 showed accelerated cell growth and validated transcriptional down-regulation of E-prote2021-01-01T00:00:00Z2021 Mar2026-05-03T08:53:16.089Z2021-03-09T08:17:39ZS-EPMC79331463366436810.1038/s41598-021-84647-2