DM Notes 3.31.16
Genes that interact with TEAD3 (hippo):
- STUB1: protein homodimerization, ligase activity. Proteasomal degradation. Misfiled protein binding.
- VGLL4:Transcription cofactor vestigial-like protein 4. Competes with YAP for binding TEADs. Acts as a tumor/growth suppressor, inhibits activity of YAP-TEAD transcriptional complex.
- GTPBP8: GTP binding, ferrous iron transmembrane transporter activity. GTP binding could be significant, it's an energy source in metabolic reactions (specifically for protein synthesis, gluconeogenesis).
Early genes in the pathway:
- STK3: down regulated across the board. Encodes serine/threonin protein kinase, acts as a growth suppressor. "Cleavage of the protein product by caspase removes the inhibitory C-terminal portion. The N-terminal portion is transported to the nucleus where it homodimerizes to form the active kinase which promotes the condensation of chromatin during apoptosis." Involved in the MAPK signaling pathway-- communicates signal from receptor on surface of cell to DNA in nucleus of cell. Defect in MAPK can lead to uncontrolled cell growth. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation
- WWC1: regulates Hippo pathway, not much further info
- NF2: probable regulator of Hippo pathway, production of merlin protein. Merlin controls cell shape, cell movement, communication between cells. Merlin functions as tumor suppressor (prevents cells from growing/dividing too fast).
- Merlin protein: tumor suppressor, found at adherens junctions, associated with contact-mediated growth inhibition.
- FRMD6: human orthologue of Expanded in drosophila. FRMd6 causes increase in phosphorylation of core Hippo signaling pathway LATS1 and YAP. Activates kinase cassette.
- FRMD1 parallel of FRMD1
MAPK pathway: cell proliferation, differentiation, development, transformation, apoptosis.
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