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transcription of S phase genes

c-maf

Transcription factor, transactivates il-4 promoter

rel

Nuclear protein

mll (htrx) (all-l) Transcription factor mll (htrx) (all-l) Transcription factor tcl-5 (tal-l) Helix-loop-helix transcription factor

Function not grouped

ß-catenin hoxll (tcl-S) tcl-2 (rhom 2) (atl) hpcl bmi-l pttg bcas-l (nabcl )

Key component of cell-cell adhesive junctions, associates with Cadherin, WNT signal transduction, APC plus GSK-3ß regulate the level of free ß-Catenin, binds to TCF and LEF transcription factors to alter gene expression Homeobox protein

Possibly identical to ski, abl2, or trk Lymphoma

Securin, binds to Separin

T-cell lymphomata Acute myeloid leukemia

Bladder cancer, colon cancer, pancreas carcinoma, leukemia Lung cancer, ovarian cancer, colon cancer, pancreas cancer Thyroid cancer, pituitary cancer Follicular lymphoma Prostate cancer

Hepatocellular carcinoma

Parathyroid adenoma B-cell lymphoma

Breast cancer, head and neck cancer Melanoma, pancreas cancer

Breast cancer

Osteosarcoma, soft tissue sarcomas

Hodgkin lymphoma, anaplastic large cell lymphoma Osteosarcoma Lymphoma

Burkitt lymphoma, leukemia, breast cancer, stomach cancer, lung cancer Neuroblastoma, glioblastoma Lung cancer Pre-B-cell ALL

Lung cancer, breast cancer Colorectal cancer, skin cancer

Multiple myeloma B-cell lymphoma

Acute myeloid leukemia, acute lymphoid leukemia T-cell leukemia, stem cell leukemia, T-cell acute leukemia

Colon cancer, melanoma

T-cell leukemias T-cell leukemias

Hereditary prostate cancer

Pituitary tumor Breast cancer

(continued)

Table 3.A. (continued)

(B) Tumor suppressor genes

Receptors dcc Membrane Adhesin-like protein, receptor for Nectrin-1

ptc Represses transcription of genes encoding tgf-p, wnt class genes, and ptc itself rara Retinoic acid receptor, nuclear hormone receptor, terminal myeloid and granulocytic differentiation, transactivates p21CIP1/WAF1 Signal transduction molecules associated with growth factor receptors Inactivation of G-Protein-GTP signal nf-1 GTPase-activating protein, inactivation of RAS, inhibition of ras tsc2 Tuberin, activation of GTPase rassf1A RAS association domain family protein rccl RAN-GEF

Cytoskeleton structure apc Communication between cell surface and microtubules,

GSK3ß substrate, binds to ß-Catenin in WNT signaling pathway, blocks progression to S phase of cell cycle nf2 Cytoskeletal protein Merlin pten (mmacl) Homology to Tensin, tyrosine phosphatase, dephosphorylates Focal Adhesion Kinase, inhibits cell migration and Integrin-mediated cell spreading, is tyrosine phosphorylated upon Integrin-mediated cell adhesion, dephosphorylates phosphatidylinositol-3,4,5-trisphosphate thus preventing the activation of PKB

fhit Possible Diadenosine Triphosphate Hydrolase, binds Tubulins and promotes microtubule assembly lung cancer, breast cancer Blockage of Cyclin-CDK activity chk2 Kinase may phosphorylate P53, cell cycle checkpoint cdknlA (wafllcipl) Binding to and inhibition of CDK2 and CDK4, activated (p21) by P53, inhibits DNA synthesis when complexed with PCNA, transcription induced by STAT1 cdknlB Inhibition of CDKs

cdkn2A Cyclin-Dependent Kinase Inhibitor 2A

(mtsl) Multiple Tumor Suppressor 1

(pl6) Inhibitor of CDK4 and CDK6

cdkn2B (mts2) Inhibitor of Cyclin-Dependent Kinases

(pl5'NK4b)

ppp2rlB ß form of the serine/threonine Protein Phosphatase 2A, down-regulates MAP Kinase cascade, inhibits nuclear Telomerase activity

Transcription factors p53 Transcription factor, stimulates transcription of p2l, cell cycle regulator, is phosphorylated by CDK and Casein Kinase, induces apoptosis via transport of CD95 from the Golgi complex p73 Transcription factor, cell cycle regulator, apoptosis, only 1 copy active due to imprinting wtl Transcription factor

Colon carcinoma, non-Hodgkin lymphoma, ovarian carcinoma Basal cell carcinoma, medulloblastoma, meningioma Acute promyelocytic leukemia

Neurofibromatosis Recklinghausen, pheochromocytoma, myeloid leukemia Astrocytoma, rhabdomyosarcoma Medulloblastoma, nasopharyngeal cancer, lung cancer Mantle cell lymphoma

Familial adenomatous polyposis, colon cancer, stomach cancer, medulloblastoma

Acoustic neuroma, meningioma, glioma, ependymoma, schwannoma Endometrial cancer, cancer, glioblastoma, breast cancer, kidney cancer, brain cancer, prostate cancer, thyroid cancer, pancreas cancer

Stomach cancer, colon cancer, esophagus cancer, cervical cancer

Breast cancer, brain cancer, leukemia Leukemia, lung cancer

Osteosarcoma, prostate cancer

Melanoma, lung cancer, medulloblastoma, pancreas carcinoma, leukemia, lymphoma

Acute lymphoblastic leukemia, lung cancer, melanoma, glioma Lung cancer, colon cancer

Osteosarcoma, breast cancer, brain tumor, Li-Fraumeni syndrome, pancreas carcinoma, small cell lung cancer

Neuroblastoma

Wilms tumor, nephroblastoma

(continued)

Table 3.A. (continued)

brg1

Negative regulation of transcription factors E2F-DP1, cell cycle regulation, activity regulated by phosphorylation (low in G0/G1, high in Gj/S) Component of the SWI-SNF chromatin remodeling complex, inhibition of proliferation through interaction with RB pancreas cancer Negative regulation of transcription factor Elongin dpc4 Signal transduction that inhibits cell division,

(smad4) signal transduction of TGF-P-like ligands, growth inhibitory signals ing1 Four splice variants 47 kD, 33 kD, 27 kD, 24 kD, cell cycle arrest in G1 by transactivation of p21WAF1CIP1 and down regulation of cyclin Bt in the presence of P53, apoptosis, transcriptional coactivator klf6 Zinc finger transcription factor, up-regulates p21CIP1jWAF1

independently of P53 ctcf Eleven zinc finger transcription factor, represses myc promoters, regulates expression of arf, pim1, plk, igf2 dmp1 Transcriptional activation of p14ARF

pml Nuclear RING finger protein, necessary for the retinoic acid-mediated transactivation of p21CIP1jWAF1, contributes to terminal myeloid differentiation mxi1 Competition with MYC for MAX, competition with MYC

for consensus DNA-binding sites, recruitment of transcriptional corepressors noey2 Down-regulation of cyclin D1 promoter activity, induction of p21CIP1/WAF1

Inducers of cell death dapk Death-Associated Protein Kinase, mediator of apoptotic signals wwox (fox) (wox1) Down-regulation of bcl-2 and bcl-xL, up-regulation of p53, enhancement of TNF cytotoxicity bax Promotion of apoptosis, P53-independent tumor suppression beclin-1 60 kD BCL-2 interacting coiled-coil protein, promotes autophagy

Function not grouped riz1

tsc1 men1

ext1 syk s100A2 hic-1

RB-interacting zinc finger, frequent frameshift mutations in cancers with microsatellite instability, contains RB binding motif and nuclear hormone receptor binding motif Hamartin

Cofactor in Histone Methyl Transferase complex

Polymerizes heparan sulfate Tyrosine kinase

Nuclear calcium-binding protein

Located on chromosome 17p13.3, frequently hypermethylated

Retinoblastoma, osteosarcoma, small cell lung cancer, bladder cancer, breast cancer, prostate cancer, cervical carcinoma prostate cancer, breast cancer, lung cancer von Hippel-Lindau disease, renal carcinoma pheochromocytoma Pancreas cancer, brain Cancer, colorectal cancer

Esophageal squamous cell cancer, head and neck cancer

Prostate cancer

Breast cancer, prostate cancer, Wilms tumor

Lymphoma

Acute promyelocyte leukemia

Prostate adenocarcinoma, T-cell leukemia, glioblastoma, squamous skin carcinoma

Breast cancer, ovarian cancer

Lymphoma, bladder cancer

Esophageal cancer, gastric cancer, ovarian cancer

Colon cancer, leukemia Breast cancer, ovarian cancer

Colorectal cancer, gastric cancer, endometrial cancer

Facial angiofibroma

Multiple endocrine neoplasia type 1, pancreas cancer, leukemia Chondrosarcoma Breast cancer Breast cancer, lung cancer Medulloblastoma, lung cancer, colon cancer in cancer

It is controlled by their nuclear localization sequences.

- The Cyclin/CDK complex requires phosphoryla-tion on threonine for activation. The CDKs are phosphorylated, and thus activated by CDK-Activating Kinases (CAK).

- A level of CDK activation is the dephosphoryla-tion of its ATP-binding site by dual specific tyrosine and threonine Phosphatases of the CDC25 family.

Quiescence. In the absence of growth factors, cells cease proliferation in the G1 phase of the cell cycle and enter G0 [Cooper 1999]. The exposure of G0-arrested cells to growth factors re-activates cell cycle progression by inducing transcriptional activity.

restriction point restriction point

Figure 3.1.1.A, Components of the cell cycle. Promoting factors are depicted on green background outside the cell cycle, while inhibitory factors are shown on red background inside the cell cycle. Cells in G0 have exited the cell cycle, but can be stimulated to reenter it by growth factors.

The transcription of early response genes is induced within a few minutes and is not dependent on protein synthesis, because the required transcription factors are present in G0 cells and are activated by posttranslational modifications, such as phosphory-lation. Many of the early response gene products, such as c-FOS and c-JUN, stimulate the expression

Table 3.1.1.A, Cyclins in the cell cycle. Progression through the cell cycle is tightly controlled by Cyclins, Cyclin-Dependent Kinases (CDKs), and CDK-Activating Kinases (CAKs). They act in a hierarchical order, with CAKs activating CDKs, which in turn activate Cyclins. Individual Cyclins act selectively at specific stages of the cell cycle

Table 3.1.1.A, Cyclins in the cell cycle. Progression through the cell cycle is tightly controlled by Cyclins, Cyclin-Dependent Kinases (CDKs), and CDK-Activating Kinases (CAKs). They act in a hierarchical order, with CAKs activating CDKs, which in turn activate Cyclins. Individual Cyclins act selectively at specific stages of the cell cycle

Cyclin

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