Flashcards in Gene Expression Shred Fest III LO Deck (17)
what are 5 ways in which sequence specific DNA binding proteins are regulated?
1. alter conformation of DNA binding protein by ligand binding
2. regulate entry into the nucleus
3. regulate the amount of transcription factor in the cell
4. regulate DNA binding
5. phosphorylate DNA binding protein to alter properties including protein degredeation, recruitment of co-activators, and DNA binding
how does estrogen cause transcriptional activation?
binds to estrogen receptor on DNA and this allows dimerization to occur (recruitment of other initiating factors)
how does tamoxifen work?
it is an estrogen antagonist. Binds to the estrogen receptor complex, causes conformational change, and causes deactivation of the gene. Can also recruit co-repressors. Repressing estrogen activated genes slows the growth of cancer (breast)
how do hormones affect the movement of transcription factors from cytoplasm to the nucleus?
hormone binds to the ligand binding domain of the DNA binding domain. Hormone binding causes conformational change causing disassociation of original ligand (which prevented DBD from entering nucleus) and then DNA binding domain can enter nucleus
what is a common way to signal degredation of a protein?
phosphorylation or ubiquination of a protein
how does aspirin inhibit inflammatory response?
inflammatory response regulated by the presence of IkB, when IkB is phosphoylated it is degraded and DNA binding domain can enter nucleus and activate transcription of inflammatory response, aspirin works in a similar pathway to block the phosphorylation and ultimate degredation of IkB
how does calcineurin regulate nuclear entry of NF-ATc?
calcineurin dephosphorylates NF-ATc which allows it to enter the nucleus and bind to a similar protein to activate transcription. When NF-ATc is phosphorylated, it cannot enter the nucleus
what is the function of adenomatous polyposis coli (APC) in the Wnt sinaling pathway?
causes phosphylation of beta-catenin thus causing its degredation
what is the function of beta-catenin?
when enters nucleus, activates Wnt responsive genes which are involved in colon growth
what happens when APC is mutated and does not function?
leads to large amount of polyps in childhood and eventually colon cancer
why is p53 important?
regulator in cell replication and cell death
what is p53 known as?
the guardian of the genome because it activates mechanisms to protect the correctness of the genome
what does MDM2 do?
binds to activation domain of p53 and then targets it for destruction
what would high levels of MDM2 do in a cell?
create tumors because MDM2 causes degredation of p53
how do Id proteins regulate DNA binding?
Id proteins negatively regulate DNA binding by promoting heterodimerization of helix-loop-helix domains. This heterodimerization causes a loss of the basic domain and thus it cannot bind to the DNA
what does phosphorylation of CREB do?
promotes transcription by allowing recruitment of CBP/Pol II