Define Explain the role of CDK inhibitors. If cyclin-CDK com-plexes are necessary to allow regulated progression through the eukaryotic cell cycle, what would be the physiologicalrationale for CDK inhibitors?

When challenged with a low oxygen environment, knownas hypoxia, the body produces a hormone called erythropoietin(EPO), which then stimulates red blood cell production tocarry more oxygen. Transcription of the gene encoding EPO isdependent upon the hypoxia-inducible factor (HIF), which is atranscriptional activator. However, HIF alone is not sufficientto activate EPO. For example, Wang et al. (2010. PLOS ONE 5:e10002) showed that HIF recruits another protein called p300to an enhancer for the EPO gene. Furthermore, deletion of p300significantly impaired transcription of the EPO gene in responseto hypoxia. Given that p300 is a type of histone acetyl transferase,how might p300 influence transcription of the EPO gene?

In contrast to their similar brain abnormalities,newborn mice deficient in Apaf1 or caspase-9 have dis-tinctive abnormalities in their paws. Apaf1-deficient micefail to eliminate the webs between their developing digits,whereas caspase-9-deficient mice have normally formeddigits (Figure Q18–1). If Apaf1 and caspase-9 function inthe same apoptotic pathway, how is it possible for thesedeficient mice to differ in web-cell apoptosis?

The mechanisms that “trigger” micrometastases to develop into macrometastases (which can be clinically detected) are still poorly understood. However, elucidating these pathways could offer valuable insights into the long term treatment of cancer patients. Interestingly, the efficiency of this process is believed to be very low (indeed, many patients exhibit micrometastases that never develop into full blown clinical metastases). Which mechanism has a stronger influence on the outcome of colonization? What is the main driver leading to the development of macrometastases from micrometastases?