The implication is that the defects were due to one or more ��non-ribosomal�� functions of DdS4 being compromised. Eukaryotic ribosomal protein-encoding genes are known to have pleiotropic roles. They are associated with transcription, splicing, translation and DNA repair; their deficiency has been linked to developmental disorders in humans, fruit flies and plants. In fish, ribosomal protein genes act as haplo-insufficient tumour suppressors and are likely to be involved in regulating normal development. Interestingly, a knock-down mutation of the zebrafish S4 gene leads to developmental defects, predominantly of neurological origin. S19 deficiency in zebrafish leads to hematopoietic and developmental abnormalities due to dysregulation of delta Np63 and p53. L13a, a ribosomal protein binds to the 39-UTR of ceruloplasmin mRNA and inhibits its translation – but only after it has been phosphorylated and released from the Ibrutinib ribosome. Of particular interest to our study, RPL41, a ribosomal large subunit protein, associates with several cytoskeleton components including tubulin b, Y and myosin IIA. In the case of D. discoideum, it has been reported that S4 binds inositol 6-phosphate. The implications remain unknown, but the finding suggests that DdS4 also has a role in the plasma membrane or in signal transduction. DdS4 is rather different from ScS4 in sequence; the latter groups with other fungal S4 proteins. Sequence analysis points to similar domain architectures; a largely conserved N-terminus region and significant variations in the Cterminal end. Some residues are conserved between ScBem1p homologues and DdS4 but vary between DdS4 and other S4��s. These features explain why DdS4, but not ScS4, can substitute for the absence of one of the proteins in the bud site selection complex in yeast. Since DdS4 can compensate for the lack of ScCdc24p, ScCdc42p or ScBem1p in yeast, one possibility is that DdS4 could substitute for any of these proteins in the complex. However, this is functionally difficult to envisage. On the other hand, completely unrelated proteins can substitute for a scaffold protein since scaffolding functions are flexible and promiscuous. Given that, we conjecture that in spite of significant differences in the amino acid sequences overall, DdS4 can act as a surrogate for ScBem1p; and the rescue by DdS4 of Sccdc24-4 and Sccdc42 is a consequence of DdS4 functioning as a scaffold protein in yeast. Being temperature-sensitive, Sccdc24-4 and Sccdc42-1 are likely to be missense mutations. AZ 960 Though present in the cell at the restrictive temperature, the corresponding proteins will be unable to function normally because most molecules have an inappropriate conformation. When overexpressed, a surrogate scaffold protein can bind the misfolded protein and permit a functional complex to form.