Strong ubiquitination activity is detected only when Bmi1, wild-type or mutant, are combined with functional Ring1A (Fig. 6D).
This is consistent with our data generated in yeast demonstrating that while the S303A mutation did activate human HSF1-dependent yeast growth, this was further enhanced when the S303A HSF1 mutant was combined with the LZ4m mutation (Figure 3A).
Interestingly, the D180-215 mutant only induced approximately 40% cell death, whereas 85% cell death was observed when the mutant was combined with mTRAIL treatment.
However, when this mutant was combined with dot1Δ, it was defective in G2/M checkpoint activation similar to the dpb11Δ C mutant.
The requirement of emasculation is negated when the pop1/cer6-1 - fwf-1/arf8-4 double mutant is combined with the ats-1/kan4-1 mutant, which has a lesion in ovule integument development [ 2].
When the spt mutant is combined with mutations in the INDEHISCENT (IND) gene [ 9], the effect on style and stigma development is significantly enhanced reflecting the synergistic activities of these two basic helix-loop-helix transcription factors [ 15].
Therefore, MPA phenotypes of combinations of GTF alleles and Pol II mutants appeared additive or suppressive depending on the nature of the allele class: when upstream shifting alleles were combined, MPA sensitivity was exacerbated; when an upstream shifting mutant was combined with a downstream shifting mutant, MPA sensitivity was alleviated.
Moreover, rapid quench-flow kinetic analyses confirmed wild-type rates of E2-to-E3 Ub transfer for these mutants, and also observed 43-fold rescue in the rate of Ub ligation to Sna3C when the defective F806L mutant was combined with L506F mutation.
Viable flies were obtained when the dfoxo Δ94 mutant was combined with either overexpression of a dominant negative form of the Drosophila insulin receptor (UAS-InRDN) under the control of the ubiquitous and constitutive daughterless-GAL4 driver (daGAL) or late ablation of the mNSCs by the expression of UAS- reaper (UAS-rpr) under the control of the InsP3-GAL4 drInsP3GALsP3GAL).
Consistent with this, substitution of Phe54 at the tip of the HCDR2 loop of CR6261 with leucine or alanine reduced binding in relation to hydrophobicity, and additive decreases in binding were observed when CR6261 mutants and HA mutants were combined (Fig. 9b).
