Haynes Lab:Notebook/Synthetic Biology and Bioinformatics for Predictable Control of Therapeutic Gene2/2012/11/16

Genes of Focus

There is a threshold of > 10^-3
HepG2

• TBD

K562
MAP Kinase Activity
1. MAPK14

• The substrates of this kinase include transcription regulator ATF2, MEF2C, and MAX, cell cycle regulator CDC25B, and tumor suppressor p53, which suggest the roles of this kinase in stress related transcription and cell cycle regulation, as well as in genotoxic stress response.

2. MAPK9

• Involved in UV radiation induced apoptosis, thought to be related to the cytochrome c-mediated cell death pathway
• This kinase blocks the ubiquitination of tumor suppressor p53, and thus it increases the stability of p53 in nonstressed cells

3. MAPK10

• Through its phosphorylation and nuclear localization, this kinase plays regulatory roles in the signaling pathways during neuronal apoptosis

Phosphotransferase activity, alcohol group as acceptor
4. RET

• This gene plays a crucial role in neural crest development, and it can undergo oncogenic activation in vivo and in vitro by cytogenetic rearrangement.
• Mutations in this gene are associated with the disorders multiple endocrine neoplasia, type IIA, multiple endocrine neoplasia, type IIB, Hirschsprung disease, and medullary thyroid carcinoma.

5. FGFR4

• This particular family member preferentially binds acidic fibroblast growth factor and, although its specific function is unknown, it is overexpressed in gynecological tumor samples, suggesting a role in breast and ovarian tumorigenesis.

6. CDKN1A

• The encoded protein binds to and inhibits the activity of cyclin-CDK2 or -CDK4 complexes, and thus functions as a regulator of cell cycle progression at G1.
• The expression of this gene is tightly controlled by the tumor suppressor protein p53, through which this protein mediates the p53-dependent cell cycle G1 phase arrest in response to a variety of stress stimuli.
• Plays a regulatory role in S phase DNA replication and DNA damage repair.
• May be instrumental in the execution of apoptosis following caspase activation.

SK-N-SH RA
Signaling receptor activity
1. KIT

• This gene encodes the human homolog of the proto-oncogene c-kit. C-kit was first identified as the cellular homolog of the feline sarcoma viral oncogene v-kit.
• Mutations in this gene are associated with gastrointestinal stromal tumors, mast cell disease, acute myelogenous lukemia, and piebaldism.

2. TNFRSF11A

• TNF-receptor superfamily (tumor necrosis factor)

3. EGFR

• Mutations in this gene are associated with lung cancer.

Sequence-Specific DNA Binding
4. WT1

• It is mutated in a small subset of patients with Wilm's tumors

5. HLF

• Chromosomal translocations fusing portions of this gene with the E2A gene cause a subset of childhood B-lineage acute lymphoid leukemias.

6. BCL6

• This gene is found to be frequently translocated and hypermutated in diffuse large-cell lymphoma (DLCL), and may be involved in the pathogenesis of DLCL.