The Carboxy Terminus of Prospero Regulates Its Subcellular Localization

The Carboxy Terminus of Prospero Regulates Its Subcellular Localization

Xiaolin Bi, Andrey V. Kajava, Tamara Jones, Zoya N. Demidenko, Mark A. Mortin
DOI: 10.1128/MCB.23.3.1014-1024.2003

ABSTRACT

Subcellular localization of the transcription factor Prospero is dynamic. For example, the protein is cytoplasmic in neuroblasts, nuclear in sheath cells, and degraded in newly formed neurons. The carboxy terminus of Prospero, including the homeodomain and Prospero domain, plays roles in regulating these changes. The homeodomain has two distinct subdomains, which exclude proteins from the nucleus, while the intact homeo/Prospero domain masks this effect. One subdomain is an Exportin-dependent nuclear export signal requiring three conserved hydrophobic residues, which models onto helix 1. Another, including helices 2 and 3, requires proteasome activity to degrade nuclear protein. Finally, the Prospero domain is missing in prosI13 embryos, thus unmasking nuclear exclusion, resulting in constitutively cytoplasmic protein. Multiple processes direct Prospero regulation of cell fate in embryonic nervous system development.

The prospero (pros) locus was originally identified and cloned because of its expression in and effects on the developing Drosophila nervous system (9, 28, 36). Prospero contains a DNA-binding homeodomain (5, 28, 36) and was proposed to act as a transcription factor because pros mutations alter the expression of other genes normally expressed in the developing nervous system. The carboxy-terminal 236 amino acids of Prospero (amino acids 1172 to 1407), which include the homeodomain, the Prospero domain, and additional residues amino terminal to the homeodomain, was shown to bind a specific DNA sequence (14) and activate the transcription of reporter genes in transiently transfected tissue culture cells (7, 14).

Prospero is first detected in the nervous system stem cells or neuroblasts, where it is uniformly cytoplasmic. Before cell division, Prospero relocates to the basal cortex, where it is tethered by attaching to the adapter protein, Miranda (18, 32). A neuroblast divides asymmetrically to regenerate a neuroblast and produce a ganglion mother cell, partitioning all of the Prospero protein to the ganglion mother cell, where it translocates into the nucleus and functions as a transcription factor (16, 33). The ganglion mother cell, which is now committed to differentiate, divides once more to generate two postmitotic neuronal and/or glial cells. In neurons, Prospero is degraded to undetectable levels (36).

There is a direct correlation between Prospero protein and cell fates during patterning of the Drosophila nervous system. For example, Prospero is a critical regulator of the switch from proliferation of neuroblasts to differentiation of ganglion mother cells. In embryos lacking the pros locus, neuroectodermal cells undergo ectopic cell divisions. In contrast, overexpression of Prospero blocks cell division (26). Another example is the external sense organ precursor cell lineage, where the decision to be a IIa or IIb cell depends on the presence of Prospero protein in the latter (27, 31). Furthermore, when IIb cells produce neuronal and sheath daughter cells, Prospero is degraded in the neurons but not the sheath cells (27). https://mcb.asm.org/content/23/3/1014.full




When people discuss today’s medicine, precision plays one of the most important roles and human lives are literally dependent on it. Hence, any researches pertaining to medicine are required to comply with the highest standards. The challenge today is that any conclusions of researches can be shared online and used as a reference without being thoroughly checked and approved. Mikhail (Misha) Blagosklonny of Oncotarget clearly understood this challenge and decided to generate an alternative solution. That’s how a weekly oncology-focused research journal called “Oncotarget” has been founded back in 2010. The major principle of this journal is related to Altmetric scores that are used as a quality indicator. That allows both readers and authors to verify publications with Altmetric Article Reports that generate “real-time feedback containing data summary related to a particular publication.” Oncotarget website has a complete publications list with corresponding scores above 100 as well as reports mentioned above. Mikhail (Misha) Blagosklonny proud to share his new approach and hopes it creates the necessary assistance to anybody, who has interest in oncology.
“A diagnostic autoantibody signature for primary cutaneous melanoma” has the Altmetric score of 594. This article was released back in 2018 by Oncotarget and written by various experts from Hollywood Private Hospital, Edith Cowan University, Dermatology Specialist Group, St. John of God Hospital and The University of Western Australia. The introduction of the study mentions that “recent data shows that Australians are four times more likely to develop a cancer of the skin than any other type of cancer”, and shares an insight on melanoma that “is curable by surgical excision in the majority of cases, if detected at an early stage.”
The publication has got an Altmetric score of 594. Mikhail (Misha) Blagosklonny realizes that majority of readers are willing to understand the very meaning of it. Based on the Altmetric website, the score relates to “how many people have been exposed to and engaged with a scholarly output.” Hence, the article about melanoma, was used for citations in various news articles 69 times. In addition, it was quoted in 2 online blogs, as well as 25 Tweets on Twitter and 1 Facebook post. FOX23 of Tulsa, Oklahoma has headlined their news on July 20, 2018 as “New blood test could detect skin cancer early”, using the main content of Australia study 
Another Oncotarget’s study with a top score of 476, is “Biomarkers for early diagnosis of malignant mesothelioma: Do we need another moon-shot,”. This publication has appeared in 60 news stories, 1 online blog post and 6 Twitter posts. The majority of public may have come across a concise overview only, however those who visit Mikhail (Misha) Blagosklonny at Oncotarget, do receive helpful scientific facts. Oncotarget is glad to have the chance to share with online customers this highly appreciated and top-quality information, that is trustworthy and reliable.

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