7.342: Week 11 Questions

Post discussion, questions, or comments about the Week 10 course material here.

Amber

Okada et al

I don't really understand Figure 4C, the Wright-Giemsa staining.

Grignani et al

In figure 1, what is the difference between the NB4 and U937 cells?

Elizabeth

Okada et al

I feel like their leap from understanding that H3-K4methyltrasderase activity is lost to compensating with hDOT1L is a bit unclear. How is it that hDOT1L is capable of doing this?

Grignani et al

In figure 1a and 1c I thought it was pretty sweet how they simply showed that CoRbox of RARalpha is necessary for the interaction between PML-RARalpha and N-CoR, and that N-CoR is necessary for the recruitment of histone deacetylase.

Georgi

Grignani et al.

How successful would and HDAC inhibitor therapy be? How far have they reached with this?

Okada et al.

What is AF-10 normally doing in the cell?

Holly

Okada et al

How did they select the proteins to use as prey in the yeast two-hybrid screening? What other proteins did they screen?

Grignani et al

One possible strategy to treat PLZF leukaemia might be to inhibit the binding of N-CoR to PLZF (using an antagonist specific to this site)? How might you go about designing a molecule that would do this?

Kathy

Okada: Their explanation for why Figure 3E RNAi MLL-AFX showed 0 colonies seems a bit dodgy, since it could also be that the experiment didn't go well? And if their explanation is correct (that a certain level of hDOT1L is required for survival), then their therapeutic goal of curing MLL by inhibiting hDOT1L seems unlikely, since the dose would have to be just right so as not to kill the human as well.

Grigani: What types of drug design approaches could be taken to solve a problem like this--where the target has two very similar domains, but only one of them should be targetted?

Manpreet

Grigani et al:

Fig. 3b - The text says that constructs 6 and 7 demonstrate that the region 2158 - 2239 are required for optimal binding. Construct 11 contains this region, but still has a very low percentage of PZLF bound.

Okada et al: Fig. 2 - I don't understand why they show colocalization with staining instead of showing coimmunoprecipitation (as they do in Fig. 1)

Zak

.