Madura - Hif 1 and Altitude

Question 1

Hif-1 Degradation

Answer 1

Mediated by VHL binding, which causes ubiquitination and degradation. VDU2 can dismantle Ub chain if Hif-1 activation becomes necessary.
-Von Hippel Tumor Suppressor: Hif-1 binds VHL to remain silent. In mutation, fails to bind, Hif-1 goes off to activate stuff inappropriately

Question 2

PDH-1,2,3

Answer 2

Puts an OH group on Hif-1 so that it can be recognized by VHL for degradation. Disactivated under hypoxic conditions by ubiquitination, as is VHL. PDH also inhibited by lack of Fe2+

Question 3

Ubiquitin in Inflammation response

Answer 3

1) Cleaves p105–>p65+50
2) Activating kinase complex (to phosphorylate IkBa)
3) Label IkBa for destruction, allowing inflammation pathway

Question 4

Mir-210

Answer 4

Micro-RNA that is activated by hypoxia. Shuts down normoxia genes

Question 5

mTOR- S6 Kinase Pathway

Answer 5

During hypoxia, translation ceases, but mTOR-S6 kinase causes selective Hif-1 translation mRNA

Question 6

mTOR/proteosome inhibitors in cancer therapy

Answer 6

mTOR: Rapamycin and Everolimus
Proteosome: Bortezomib and Carfilzomib

Question 7

Hif-1 Subunits

Answer 7

Heterodimer between an alpha and beta. 3 alphas in cytosol, 1 beta in nucleus. For hypoxia response, alpha must enter nucleus and bind beta