1. NF-  B SOLID TUMORS HEMATOLOGICAL MALIGNANCIES Multiple Myeloma Mantle Cell Lymphoma MALT Lymphoma Diffuse Large B-cell Lymphoma Hodgkin’s Lymphoma Myelodysplasic Syndrome Adult T-cell Leukemia (HTLV-1) Acute Lymphocytic Leukemia Acute Myeloid Leukemia Chronic Lymphocytic Leukemia Chronic Myeloid Leukemia Breast Cancer Cervical Cancer Prostate Cancer Renal Cancer Lung Cancer Colon Cancer Liver Cancer Pancreatic Cancer Esophageal Cancer Gastric Cancer Laryngeal Cancer Thyroid Cancer Parathyroid Cancer Melanoma Bladder Cancer Cylindroma Squamous Cell Carcinoma (Skin) Squamous Cell Carcinoma (Head and Neck) Oral Carcinoma Endometrial Carcinoma Ovarian Cancer Retinoblastoma Astrocytoma/Glioblastoma Figure 1 : Human cancers that have been linked to constitutive NF-  B activation

2. NF-  B Cell death and anti-proliferative effects FasL, Fas and DR4/5 p53 p21WAF1/CIP1 Proliferation CyclinD1, CyclinE, CDK2, c-MYC, TNF, IL1, IL6 Survival A1/BFL1, GADD45 , Bcl-2, Bcl-X L, TRAF1/2, XIAP, cIAP1/2, c-FLIP, A20, IEX-1L, Survivin, Telomerase, MnSOD Tumor promotion and Metastasis uPA, MMP2/9, VCAM-1, ICAM-1, ELAM-1, Kal-1, COX2, iNOS Inflammation TNF , IL1, IL8, MIP-2, MCP-1, iNOS, COX2, ICAM-1, E-Selectin Angiogenesis CXCL-1/8, IL-1/6, VEGF, IL8, HIF-1 , TNF Figure 2: NF-  B target genes involved in cancer development and progression

3. TRAF5/6 TRAF2 NIK p100 RelB TAK1 p100 RelB p50 RelA IBIB p105 CYLD MLN BTZMB CD40L BAFF CD40L BAFF Classical NF-  B Pathway Alternative NF-  B Pathway P P IKK  Innate immunity Inflammation Cell survival Lymphoid organogenesis B-cell maturation Humoral immunity PP PP p50 RelA p50 RelB p52 RelB IKK  IKK  IKK  Proteosomal degradation BTZMB p105 processing p100 processing c-IAP1 c-IAP2 TRAF3 Target genes p50 RelA Target genes p50 RelB p52 RelB c-IAP1 c-IAP2 Figure 3 : NF-  B gain- and loss-of-function mutations in multiple myeloma TRAF2

4. Figure 4: cIAPs and IAP antagonists in the regulation of NF-  B and cell death pathways Target genes p50 RelA IBIB P P IKK  IKK  IKK  Proteosomal degradation IAP antagonists c-IAP1 c-IAP2 TRAF2 TNF-  c-IAP1 c-IAP2 TRAF2 FADD Caspase-8 RIP1 Ub p100 RelB p50 p100 PP PP p100 processing TRAF2 c-IAP1 c-IAP2 Proteosomal degradation Apoptosis Caspase-3 Caspase-7 XIAP IAP antagonists Proteosomal degradation Ub p50 RelA Target genes p50 RelB p52 RelB p50 RelA p50 RelB p52 RelB IKK  TRADD TRAF3 Proteosomal degradation RelB Proteosomal degradation NIK Ub XIAP c-FLIP Bcl-2Bcl-xL c-IAP1/2 TRAF1/2 TNF-  c-FLIP A20 Apoptosis