Growth Autonomy 1

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Cyclins and cyclin dependent kinases (CDKs)
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Terms in this set (35)
SOSwhat does GRB2 bind to?- Ras activate RAF, which is at the top of a MAPK cascade - RAF activates MEK, which activates MAPK - MAPK translocates into the nucleus where it phosphorylates molecules involved in driving the cell cyclethe activation of Ras by SOS causes wat cascade of events after?- it also simultaneously activates other signalling transduction cascades that are essential for cell cycle to occur - Ras can directly bind to PI3Kwhy is Ras so important in the EGF signalling pathway?- Raf/MAPK - PI3K/Aktwhat are the 2 main pathways Ras activates?- PI3K converts PIP2 into PIP3 - this activates AKT - AKT can translocate into the nucleus to phosphorylate transcription factors and can stimulate lipid and nucleotide synthesiswhat happens after Ras binds to PI3K?- Ras activates Raf (has 3 isoforms) - Raf phosphorylates and activates MEK (has 2 isoforms) - MEK phosphorylates and activates ERK (has 2 isoforms) - ERK can translocate into the nucleus and phosphorylate TF involved in driving cell cyclewhat is the detailed pathway of the Raf/MEK/ERK pathway (Ras/MAPK)?Ras facilitates the shape change in Raf which allows it to dimerise which is the first part of Raf activationHow does Ras activate Raf?- AP-1 TFwhat is one of the key target TFs of ERK?- its a dimer composed of Fos and Jun proteinwhat is AP-1 composed of?- by phosphorylating and activating other TFs that regulate Fos and Jun expression - influences amount of available AP-1 in nucleushow does ERK induce AP-1 activity?cyclin Dactivation of AP-1 TFs induce expression of what?- induces expression of cyclin D by activation of AP-1 TFs - increases levels of the cdk inhibitor p21 promotes the assembly of cyclin D-cdk 4 complexes via interactions with p21 - reduces level of cdk inhibitor p27what does Ras effect on cell-cycle components?- prevents proteosome-mediated degradation of cyclin D - represses transcription of cdk inhibitors p21 and p27 - phosphorylates and inhibits the cdk inhibitor p21what are the effects of the PI3K/Akt signalling pathway?Rbwhat does cyclin D activate to cause the progression of the cell from G1 to S phase?it is bound to histone deacetylase (HDAC) - makes chromatin more compact and represses transcriptionhow does Rb act as a tumour suppressor preventing cell cycle- cyclin D binds to cdk4 and activates it - cdk4 phosphorylates Rb - the phosphorylation allows the Rb protein to release HDAC - allows transcription of certain proteins, including Cyclin E - but Rb is still bound to E2F, therefore E2F target genes are not transcribed - Cyclin E binds to cdk2 ad activates it - cdk2 phosphorylates R on another site, allowing it to release its grip on E2F, therefore allowing transcription of E2F geneshow does repression get removed in order for cell division to occur?they are involved in S phase involved in DNA synthesiswhat are E2F genes involved in?the Raf and Ras mutational status of the patientprior to treatment with a receptor tryosine kinase (RTK) inhibitor what is essential to determine in order to predict drug response?- they bind to extracellular domain pf receptors and stop ligand from binding - also induces immune response through ADCP, ADCC and CDChow do monoclonal antibodies work as an anti-cancer therapy?cetuximaban example of a monoclonal antibody- competitively bind to the ATP binding site in the tryosine kinase - prevent phosphorylation and subsequent signal transductionhow do small molecule inhibitors work as an anti-cancer therapy?- type 1 - type 2 - type 3what are the different categories of small molecule inhibitors- mimic hydrogen bonds presented by ATP - not very specificwhat do the type 1 small inhibitors do?- occupy nearby hydrophobic pocket in an inactive kinase and allosterically affect kinase activitywhat do the type 2 small inhibitors do?- the most specific - covalently bind specific cyteines in target kinasewhat do the type 3 small inhibitors do?