Table 5.
Up- and Down-Regulated Proteins after MK-2206 Treatment in DOHH2 and LP Cell Lines
Functional categories | In DOHH2 (GCB-DLBCL) |
In LP (ABC-DLBCL) |
||
---|---|---|---|---|
Increased | Decreased | Increased | Decreased | |
Cell cycle, checkpoint, DNA damage response, DNA replication, gene expression | Histone-H3, eEF2K, p27-Kip-1,∗ p16INK4a, 53BP1, p21,∗† Cyclin-E1,† ATM,† PARP-cleaved† | Chk1, Rb_pS807_S811, PLK1, Cyclin-B1,∗ FoxM1,∗ Rad51, Chk1_pS296, PCNA, Rb, ATR, UBAC1, GCN5L2, CDK1, MSH2, MSH6, Chk1_pS345, CDC2-p34, Chk2, Aurora-B | Pdcd4,∗ Cyclin-E1, PARP-cleaved† | Cyclin-B1,∗ PLK1, Rb_pS807_S811, FoxM1,∗ Chk1, Aurora-B, MSH2, ATR, CDC2-p34, Rb, MSH6, UBAC1, CDK1, PCNA, Chk1_pS296, ADAR1, ARID1A, Cyclin-D1∗ |
Apoptosis, autophagy | Bcl-2, Mcl-1, Puma, Bim,∗ Bad_pS112,∗ Caspase-7-cleaved,∗ Caspase-3,∗ Bax,∗ Beclin,∗ Caspase-9-cleaved,∗ FoxO3a∗ | FoxO3a_pS318_S321,∗ p53, Bid, XIAP∗ | Mcl-1, Bim,∗ Puma, Bcl-2, Caspase-7,∗ Smac, Bak, p53, Bad,∗ Caspase-9∗ | Bcl2A1 |
Signaling, cell growth, immune response | S6_pS235_S236,∗ p38_pT180_Y182, MEK1_pS217_S221, NF-kB-p65_pS536, Rictor,∗ PAR, PDGFR-β,∗ MAPK_pT202_Y204, Lck, PKC-α, PI3K-p110-α-R,∗ PI3K-p85,∗ Tuberin (TSC2),∗ PTEN,∗ Axl,∗ Caveolin-1, PREX1, PKC-β-II_pS660, PKC-α_pS657,† FAK_pY397,∗†IGFBP5,∗† SHP-2_pY542,∗† Gab2,∗† Akt∗† | Akt_pS473,∗ Akt_pT308,∗ eIF4G,∗ TTF1, 4E-BP1_pS65,∗ FAK, mTOR,∗ MEK1, c-Myc,∗ HER3_pY1289,∗ c-Met,∗ S6_pS240_S244∗† | PAR, Lck, c-Myc,∗ YAP_pS127,∗ Notch1, Pdcd-1L1,∗ PKC-α_pS657, Axl,∗ Caveolin-1, PDGFR-β,∗ Notch3, NF-κB-p65_pS536, PKC-δ_pS664, PKC-β-II_pS660 | Akt_pS473,∗ eIF4G,∗ p70-S6K_pT389,∗ MEK1, 4E-BP1_pS65,∗ PRAS40_pT246,∗ C-Raf, mTOR∗ |
Cell adhesion, gap junction, extracellular matrix, exocytosis, endocytosis, angiogenesis | Fibronectin, Connexin-43, Annexin-I, Annexin-VII, Claudin-7,† CD44-M† | TFRC, VEGFR-2∗ | Connexin-43, E-Cadherin,∗ Claudin-7, Annexin-VII, CD44, Annexin-I† | |
Metabolism, hypoxia | LDHA† | Hif-1α,∗ GSK-3b_pS9,∗ GSK-3ab_pS21_S9,∗ Hexokinase-II,∗ ACC1, ACC_pS79, GSK-3ab∗ | G6PD, ATP5A | GSK-3b_pS9,∗ GSK-3ab_pS21_S9,∗ SDHA, Gys, Hexokinase-II,∗ GSK-3ab∗ |
Protein folding | HSP27_pS82, Cyclophilin, HSP27 | HSP70 | HSP27 |
The order of proteins is according to the fold-change at 24 hours after treatment.
ABC, activated B-cell–like; DLBCL, diffuse large B-cell lymphoma; GCB, germinal center B-cell–like.
Proteins upstream or downstream of AKT signaling and Pdcd-1L1.
Proteins that showed increase only at 48 hours.