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. 2022 Feb 11;82(7):1234–1250. doi: 10.1158/0008-5472.CAN-21-1168

Figure 5.

Figure 5. MYC induces expression and activity of the proteasome in B-cell lymphoma. A and B, Gene expression profile of proteasome subunits (A) in splenic B220+ B cells from WT and from Eμ-Myc lymphomas (GSE32239), and of proteasome subunits (B) in untreated versus LPS (4 hours)-stimulated naïve B cells (GSE37222). Log2 gene expression profile of TFEB target genes is shown as a dot plot ordered on the basis of expression; each dot represents one sample, and its size corresponds to its statistical significance as shown. C–F, Proteasome activity was measured using Proteasome-Glo in WT versus Eμ-Myc B220+ BM cells (n = 6; C); WT versus Eμ-Myc pre-B cells cultured in IL7 (D); WT pre-B cells treated with vehicle or with the Myc inhibitors Myci361 or MYCMI6 for 2 hours (E); and naïve mouse splenic B cells that were untreated (MYC-Off) or LPS-stimulated (4 hours, MYC-On; F; D–F, n = 3). G, Log2 gene expression of proteasome-associated genes in Eμ-Myc lymphoma cells expressing vector or TFEBSA-ERT2 4 days after vehicle or 4-OHT treatment is shown as a dot plot ordered on the basis of expression; each dot represents one sample, and its size corresponds to its statistical significance as shown (n = 3 for each cohort). H, Proteasome activity, measured using Proteasome-Glo, in Eμ-Myc lymphoma cells expressing vector or TFEBSA-ERT2 after treatment with vehicle or 4-OHT for 4 days (n = 3). I, In vivo imaging of NOD-SCiD mice intravenously transplanted with Eμ-Myc;Eμ-rtTA2 lymphoma cells expressing either vector (GpNLuc) or TFEBSA-GpNLuc that were treated with vehicle or 0.25 mg/kg bortezomib (i.p. weekly) for 10 days. J, Average bioluminescence for treated with vehicle or bortezomib for 10 days. Statistical analysis: C–F and J, Student t tests were performed. *, P ≤ 0.05; **, P ≤ 0.01; ****, P ≤ 0.0001.

MYC induces expression and activity of the proteasome in B-cell lymphoma. A and B, Gene expression profile of proteasome subunits (A) in splenic B220+ B cells from WT and from Eμ-Myc lymphomas (GSE32239), and of proteasome subunits (B) in untreated versus LPS (4 hours)-stimulated naïve B cells (GSE37222). Log2 gene expression profile of TFEB target genes is shown as a dot plot ordered on the basis of expression; each dot represents one sample, and its size corresponds to its statistical significance as shown. C–F, Proteasome activity was measured using Proteasome-Glo in WT versus Eμ-Myc B220+ BM cells (n = 6; C); WT versus Eμ-Myc pre-B cells cultured in IL7 (D); WT pre-B cells treated with vehicle or with the Myc inhibitors Myci361 or MYCMI6 for 2 hours (E); and naïve mouse splenic B cells that were untreated (MYC-Off) or LPS-stimulated (4 hours, MYC-On; F; D–F, n = 3). G, Log2 gene expression of proteasome-associated genes in Eμ-Myc lymphoma cells expressing vector or TFEBSA-ERT2 4 days after vehicle or 4-OHT treatment is shown as a dot plot ordered on the basis of expression; each dot represents one sample, and its size corresponds to its statistical significance as shown (n = 3 for each cohort). H, Proteasome activity, measured using Proteasome-Glo, in Eμ-Myc lymphoma cells expressing vector or TFEBSA-ERT2 after treatment with vehicle or 4-OHT for 4 days (n = 3). I,In vivo imaging of NOD-SCiD mice intravenously transplanted with Eμ-Myc;Eμ-rtTA2 lymphoma cells expressing either vector (GpNLuc) or TFEBSA-GpNLuc that were treated with vehicle or 0.25 mg/kg bortezomib (i.p. weekly) for 10 days. J, Average bioluminescence for treated with vehicle or bortezomib for 10 days. Statistical analysis: C–F and J, Student t tests were performed. *, P ≤ 0.05; **, P ≤ 0.01; ****, P ≤ 0.0001.