Disease relevance of SWI5

• To test this prediction we have expressed the 89-amino-acid sequence of the domain containing the three zinc fingers of SWI5 in Escherichia coli as a cleavable fusion protein, purified under denaturing conditions and folded in vitro [1].

High impact information on SWI5

• Phosphorylation appears to be the main mechanism controlling the nuclear transport of a number of proteins, including transcription factors such as NFkappaB, c-rel, dorsal, and SWI5 from yeast [2].
• Swi5p remains at HO for only 5 min [3].
• As all three serines are phosphorylated by purified CDC28-dependent H1 kinase activity in vitro, we propose a model in which the CDC28 kinase acts directly to control nuclear entry of SWI5 [4].
• The intracellular localization of the S. cerevisiae transcription factor SWI5 is cell cycle dependent [4].
• We discovered that SWI5 is found equally concentrated in the nuclei of both mother and daughter cells at the end of anaphase, suggesting that its subsequent fate must somehow differ [5].

Biological context of SWI5

• SWI5 encodes a zinc-finger protein required for expression of the yeast HO gene [6].
• Two-hybrid experiments show that amino acids 471 to 513 of Swi5 are necessary and sufficient for interaction with Pho2 and that the SWI5* point mutations cause a severe reduction in this two-hybrid interaction [7].
• N-terminal amino acid sequence analysis identified the Swi5 stimulatory factor as the product of the GRF10 gene, which encodes a yeast homeodomain protein [6].
• Swi5 accumulates in the cytoplasm during S, G2, and M phases of the cell cycle but enters the nuclei at late anaphase [8].
• We have shown that high SIC1 transcript levels at late M phase depend on Swi5 [8].

Anatomical context of SWI5

• The yeast transcription factors Ace2p and Swi5p regulate the expression of several target genes involved in mating type switching, exit from mitosis and cell wall function [9].
• This regulation is vital for mother-cell specificity since constitutive transcription of SWI5 causes daughter cells to switch their mating types [10].
• Ash1p, which only accumulates in daughter cell nuclei, binds to HO soon after Swi5p and aborts recruitment of Swi/Snf, SAGA, and SBF [3].

Associations of SWI5 with chemical compounds

• In this work we describe an important additional layer of complexity to the current model by identifying a connection between Swi5 and the Mediator/RNA polymerase II holoenzyme complex [11].

Physical interactions of SWI5

• Grf10 protein purified from a bacterial expression system binds DNA cooperatively with Swi5 in vitro [6].
• Interactions between Pho85 cyclin-dependent kinase complexes and the Swi5 transcription factor in budding yeast [12].
• Analysis of CTS1 promoter fragments inserted into a heterologous promoter identify a sequence 90 bp away from the Ace2p binding sites which is required to prevent activation by Swi5p through these binding sites [13].
• We identified a gene with a Swi5-binding site in the promoter that encoded a protein with high homology to Pcl2, a cyclin-like protein that associates with the Cdk Pho85 [14].
• The SWI5 gene encodes a zinc finger DNA-binding protein required for the transcriptional activation of the yeast HO gene [15].

Regulatory relationships of SWI5

• We have shown previously that the Swi5 transcription factor regulates the expression of the SIC1 Cdk inhibitor in late mitosis [14].
• SIN3 was first identified by a mutation which suppresses the effects of an swi5 mutation on expression of the HO gene in Saccharomyces cerevisiae [16].
• A version of the HO promoter that has lost its dependence on Start is nevertheless still strongly cell cycle regulated and is activated when SWI5 moves into the nucleus [5].
• The role of phosphorylation and the CDC28 protein kinase in cell cycle-regulated nuclear import of the S. cerevisiae transcription factor SWI5 [4].
• EGT2 gene transcription is induced predominantly by Swi5 in early G1 [17].

Other interactions of SWI5

• Fkh2 protein is associated with the promoters of CLB2, SWI5 and other genes of the cluster [18].
• Our data suggest that cell cycle-regulated nuclear accumulation of Swi5 is responsible for the burst of SIC1 transcription at the end of anaphase [8].
• We also found that overexpression of SWI5 caused cell lethality in a pho85 deletion strain [12].
• This suggests that one function of SIN5 is to prevent ACE2, a SWI5 homolog, from activating HO expression [19].
• SWI5 encodes a transcription factor paralogous to ACE2 [20].

Analytical, diagnostic and therapeutic context of SWI5

• We performed both biochemical and genetic tests to discover the biological significance of the interaction between Pcl2 and Swi5 seen in the two-hybrid assay [12].

References