Disease relevance of SCP160

• Histiocytosis X (HX) is a rare disorder of Langerhans cells and most commonly occurs in children [1].
• We report a case of HX of the vulva in a 76-year-old woman that clinically simulated a yeast infection of the vulva but histologically resembled an amelanotic melanoma [1].

High impact information on SCP160

• We also show that signaling by activated Gpa1 requires direct coupling to an RNA binding protein Scp160 [2].
• DDP1 is a multi-KH domain protein homologous to the yeast Scp160 protein that is involved in the control of cell ploidy [3].
• The contribution of Scp160p to silencing is independent of its binding to the ribosome as deletion of the last two KH domains, which mediate ribosomal binding, has no effect on silencing [4].
• Disruption of SCP160 increases cell ploidy but this effect is also independent of the contribution of Scp160p to telomeric silencing as strong relief of silencing is observed in Deltascp160 cells with normal ploidy and, vice versa, Deltascp160 cells with highly increased ploidy show no significant silencing defects [4].
• These results are discussed in the context of a model in which Scp160p contributes to silencing by helping telomere clustering [4].

Biological context of SCP160

• The SCP160 gene resides on the left arm of chromosome X and codes for a polypeptide of molecular weight around 160 kDa [5].
• We have cloned a new gene, SCP160, from Saccharomyces cerevisiae, the deduced amino acid sequence of which does not exhibit overall similarity to any known yeast protein [5].
• To reconfirm scp160/eap1 synthetic lethality, we constructed a strain null for both genes, supported by an SCP160 maintenance plasmid [6].
• The multi-KH domain protein of Saccharomyces cerevisiae Scp160p contributes to the regulation of telomeric silencing [4].
• Moreover, we found that Scp160p contains a potential nuclear-export signal (NES) near its N-terminus and a potential nuclear-localization signal (NLS) between KH domains 3 and 4 [7].

Anatomical context of SCP160

• Scp160p is a multiple KH-domain RNA-binding protein in yeast known to associate with polyribosomes as an mRNP component, although its biological role remains unclear [6].
• Scp160p, an RNA-binding, polysome-associated protein, localizes to the endoplasmic reticulum of Saccharomyces cerevisiae in a microtubule-dependent manner [8].
• Accumulation of Scp160p-ribosome complexes at the ER requires the function of microtubules but is independent of the actin cytoskeleton [8].
• Scp160p (Saccharomyces cerevisiae protein involved in the control of ploidy), a polypeptide with a molecular mass of around 160 kDa, is associated with the nuclear envelope and the endoplasmic reticulum [7].
• However, no signal sequence or membrane-spanning region exists, suggesting that the Scp160 protein is attached to the cytoplasmic surface of the ER-nuclear envelope membranes [5].

Associations of SCP160 with chemical compounds

• Furthermore, we have found that Scp160p is released from polyribosomes by EDTA in the form of a large complex of> or =1300 kDa that is sensitive both to RNase and NaCl [9].
• Using sucrose gradient fractionation studies we have demonstrated that Scp160p in cytoplasmic lysates is predominantly associated with polyribosomes [9].

Physical interactions of SCP160

• Scp160p is an RNA-binding protein containing 14 tandemly repeated heterogenous nuclear ribonucleoprotein K-homology domains, which are implicated in RNA binding [8].

Other interactions of SCP160

• Finally, we probed the impact of EAP1 loss on Scp160p, and vice versa, and found that loss of each gene resulted in a significant change in either the complex associations or subcellular distribution of the other protein [6].
• These findings suggest an additional role for Gpa1 and reveal Scp160 as a component of the mating response pathway in yeast [2].
• Finally, we report that loss of Bfr1p disrupts the interaction of Scp160p with polyribosomes, thereby demonstrating that the relationship between these two proteins is functional as well as physical [10].
• The interaction of Scp160p with ribosomes depends on Asc1p [11].
• Using affinity-chromatography to isolate these complexes, we have identified two protein components other than Scp160p: poly(A) binding protein, Pab1p, and Bfr1p [9].

Analytical, diagnostic and therapeutic context of SCP160

• To determine whether the protein is able to bind to RNA, we purified Scp160p from yeast cell extract by DNA-cellulose and anti-Scp160p affinity chromatography [7].
• By immunofluorescence microscopy the Scp160 protein appears to be localized to the nuclear envelope and to the endoplasmic reticulum (ER) [5].
• Although the vast majority of Scp160p sequence consists of 14 closely spaced KH domains, comparative sequence analyses also demonstrate the presence of a potential nuclear localization sequence located between KH domains 3 and 4, as well as a 110 amino acid non-KH N-terminal region that includes a potential nuclear export sequence (NES) [12].

References