The Phylogenetic Functional Conservation of  Drosophila Seven-in-Absentia (SINA) E3 Ligase and Its Two Human Paralogs, SIAH1 and SIAH2, in  Drosophila Eye Development

2020 ◽  
Author(s):  
Robert E. Van Sciver ◽  
Yajun Cao ◽  
Amy H. Tang
Keyword(s):  
Eye Development ◽  
E3 Ligase ◽  
Functional Conservation ◽  
Seven In Absentia

scholarly journals Functional conservation of vertebrate seven-up related genes in neurogenesis and eye development.

1993 ◽  
Vol 12 (4) ◽  
pp. 1403-1414 ◽  
Author(s):  
A. Fjose ◽  
S. Nornes ◽  
U. Weber ◽  
M. Mlodzik
Keyword(s):  
Eye Development ◽  
Functional Conservation

scholarly journals Musashi and Seven in absentia downregulate Tramtrack through distinct mechanisms in Drosophila eye development

1999 ◽  
Vol 87 (1-2) ◽  
pp. 93-101 ◽  
Author(s):  
Yuki Hirota ◽  
Masataka Okabe ◽  
Takao Imai ◽  
Mitsuhiko Kurusu ◽  
Atsuyo Yamamoto ◽  
...  
Keyword(s):  
Eye Development ◽  
Drosophila Eye ◽  
Seven In Absentia

scholarly journals E3 ubiquitin ligase-mediated regulation of vertebrate ocular development; new insights into the function of SIAH enzymes

2021 ◽  
Vol 49 (1) ◽  
pp. 327-340
Author(s):  
Warlen Pereira Piedade ◽  
Jakub K. Famulski
Keyword(s):  
Protein Function ◽  
Cell Function ◽  
Developmental Stages ◽  
E3 Ligase ◽  
Critical Time ◽  
26S Proteasome ◽  
Model Organisms ◽  
Ocular Development ◽  
Seven In Absentia

Developmental regulation of the vertebrate visual system has been a focus of investigation for generations as understanding this critical time period has direct implications on our understanding of congenital blinding disease. The majority of studies to date have focused on transcriptional regulation mediated by morphogen gradients and signaling pathways. However, recent studies of post translational regulation during ocular development have shed light on the role of the ubiquitin proteasome system (UPS). This rather ubiquitous yet highly diverse system is well known for regulating protein function and localization as well as stability via targeting for degradation by the 26S proteasome. Work from many model organisms has recently identified UPS activity during various milestones of ocular development including retinal morphogenesis, retinal ganglion cell function as well as photoreceptor homeostasis. In particular work from flies and zebrafish has highlighted the role of the E3 ligase enzyme family, Seven in Absentia Homologue (Siah) during these events. In this review, we summarize the current understanding of UPS activity during Drosophila and vertebrate ocular development, with a major focus on recent findings correlating Siah E3 ligase activity with two major developmental stages of vertebrate ocular development, retinal morphogenesis and photoreceptor specification and survival.

Reciprocal antagonistic regulation of E3 ligases controls ACC synthase stability and responses to stress

2021 ◽  
Vol 118 (34) ◽  
pp. e2011900118
Author(s):  
Han Yong Lee ◽  
Hye Lin Park ◽  
Chanung Park ◽  
Yi-Chun Chen ◽  
Gyeong Mee Yoon
Keyword(s):  
Stress Responses ◽  
Molecular Mechanisms ◽  
E3 Ligase ◽  
Acc Synthase ◽  
Ethylene Biosynthesis ◽  
Cellular Protein ◽  
Dependent Manner ◽  
E3 Ligases ◽  
Seven In Absentia ◽  
Rate Limiting

Ethylene influences plant growth, development, and stress responses via crosstalk with other phytohormones; however, the underlying molecular mechanisms are still unclear. Here, we describe a mechanistic link between the brassinosteroid (BR) and ethylene biosynthesis, which regulates cellular protein homeostasis and stress responses. We demonstrate that as a scaffold, 1-aminocyclopropane-1-carboxylic acid (ACC) synthases (ACS), a rate-limiting enzyme in ethylene biosynthesis, promote the interaction between Seven-in-Absentia of Arabidopsis (SINAT), a RING-domain containing E3 ligase involved in stress response, and ETHYLENE OVERPRODUCER 1 (ETO1) and ETO1-like (EOL) proteins, the E3 ligase adaptors that target a subset of ACS isoforms. Each E3 ligase promotes the degradation of the other, and this reciprocally antagonistic interaction affects the protein stability of ACS. Furthermore, 14–3-3, a phosphoprotein-binding protein, interacts with SINAT in a BR-dependent manner, thus activating reciprocal degradation. Disrupted reciprocal degradation between the E3 ligases compromises the survival of plants in carbon-deficient conditions. Our study reveals a mechanism by which plants respond to stress by modulating the homeostasis of ACS and its cognate E3 ligases.

scholarly journals Ligand-mediated protein degradation reveals functional conservation among sequence variants of the CUL4-type E3 ligase substrate receptor cereblon

2018 ◽  
Vol 293 (16) ◽  
pp. 6187-6200 ◽  
Author(s):  
Afua A. Akuffo ◽  
Aileen Y. Alontaga ◽  
Rainer Metcalf ◽  
Matthew S. Beatty ◽  
Andreas Becker ◽  
...  
Keyword(s):  
Protein Degradation ◽  
E3 Ligase ◽  
Sequence Variants ◽  
Functional Conservation

scholarly journals Controversy regarding the functional conservation of cereblon CUL4-type E3 ligase substrate receptor

2018 ◽  
Vol 5 (4) ◽  
Author(s):  
Afua A Akuffo ◽  
Aileen Y Alontaga ◽  
Harshani R Lawrence ◽  
Nicholas J. Lawrence ◽  
Pearlie K Epling-Burnette
Keyword(s):  
E3 Ligase ◽  
Functional Conservation

scholarly journals The phylogenetic functional conservation of Drosophila Seven-In-Absentia (SINA) E3 ligase and its two human paralogs, SIAH1 and SIAH2, in Drosophila eye development

2020 ◽  
Author(s):  
Robert E. Van Sciver ◽  
Yajun Cao ◽  
Amy H. Tang
Keyword(s):  
Amino Acid ◽  
Cell Fate ◽  
Genetic Modifier ◽  
Ring Domain ◽  
Single Point Mutation ◽  
Cell Fate Determination ◽  
E3 Ligases ◽  
Fate Determination ◽  
Functional Conservation ◽  
Seven In Absentia

AbstractSeven-IN-Absentia (SINA) is the most downstream signaling gatekeeper identified thus far in the RAS/EGFR pathway that controls photoreceptor cell fate determination in Drosophila. Underscoring the central importance of SINA is its phylogenetic conservation in metazoans, with over 83% amino acid identities shared between Drosophila SINA and human SINA homologs (SIAHs). SIAH is a major tumor vulnerability in multidrug-resistant and incurable cancer. SIAH inhibition is an effective strategy to shut down the tumor-driving K-RAS/EGFR/HER2 pathway activation that promotes malignant tumor growth and metastatic dissemination. To further delineate the SINA function in the RAS/EGFR pathway, a genetic modifier screen was conducted, and 28 new sina mutant alleles were isolated via ethyl methanesulfonate (EMS) and X-ray mutagenesis. Among them, 26 of the new sina mutants are embryonic, larval, or pupal lethal, and stronger than the five published sina mutants (sina1, sina2, sina3, sina4, and sina5) which are early adult lethal. By sequencing the SINA-coding region of sinaES10, sinaES26, sinaES79, and sinaES473 homozygous mutant animals, we identified three invariable amino acid residues in SINA’s RING-domain whose single point mutation ablates SINA function. To demonstrate the functional conservation of this medically important family of RING domain E3 ligases in Drosophila, we established a collection of transgenic lines, expressing either wild type (WT) or proteolysis-deficient (PD) SINA/SIAH inhibitors of Drosophila SINAWT/PD and human SIAH1WT/PD/2WT/PD under tissue-specific GAL4-drivers in Drosophila eye, wing, and salary gland. Our results showed that Drosophila SINA and human SIAH1/2 are functionally conserved. Our bioengineered SINAPD/SIAHPD inhibitors are effective in blocking the RAS-dependent neuronal cell fate determination in Drosophila.

A Genetic Screen to Identify Components of the sina Signaling Pathway in Drosophila Eye Development

Genetics ◽  
1998 ◽  
Vol 148 (1) ◽  
pp. 277-286
Author(s):  
Thomas P Neufeld ◽  
Amy H Tang ◽  
Gerald M Rubin
Keyword(s):  
Cell Fate ◽  
Eye Development ◽  
Ectopic Expression ◽  
Genetic Screen ◽  
Cell Fate Specification ◽  
Morphogenetic Furrow ◽  
Drosophila Homolog ◽  
Drosophila Eye ◽  
Ubiquitin Conjugating Enzyme ◽  
Seven In Absentia

AbstractSpecification of the R7 photoreceptor cell in the developing Drosophila eye requires the seven in absentia (sina) gene. We demonstrate that ectopic expression of sina in all cells behind the morphogenetic furrow disrupts normal eye development during pupation, resulting in a severely disorganized adult eye. Earlier events of cell fate specification appear unaffected. A genetic screen for dominant enhancers and suppressors of this phenotype identified mutations in a number of genes required for normal eye development, including UbcD1, which encodes a ubiquitin conjugating enzyme; SR3-4a, a gene previously implicated in signaling downstream of Ras1; and a Drosophila homolog of the Sin3A transcriptional repressor.

A Genetic Screen to Identify Components of the sina Signaling Pathway in Drosophila Eye Development

Genetics ◽  
1998 ◽  
Vol 148 (1) ◽  
pp. 277-286 ◽  
Author(s):  
Thomas P Neufeld ◽  
Amy H Tang ◽  
Gerald M Rubin
Keyword(s):  
Cell Fate ◽  
Eye Development ◽  
Ectopic Expression ◽  
Genetic Screen ◽  
Cell Fate Specification ◽  
Morphogenetic Furrow ◽  
Drosophila Homolog ◽  
Drosophila Eye ◽  
Ubiquitin Conjugating Enzyme ◽  
Seven In Absentia

Abstract Specification of the R7 photoreceptor cell in the developing Drosophila eye requires the seven in absentia (sina) gene. We demonstrate that ectopic expression of sina in all cells behind the morphogenetic furrow disrupts normal eye development during pupation, resulting in a severely disorganized adult eye. Earlier events of cell fate specification appear unaffected. A genetic screen for dominant enhancers and suppressors of this phenotype identified mutations in a number of genes required for normal eye development, including UbcD1, which encodes a ubiquitin conjugating enzyme; SR3-4a, a gene previously implicated in signaling downstream of Ras1; and a Drosophila homolog of the Sin3A transcriptional repressor.

Fine structure of the retina of the giant scallop, Placopecten magellanicus

1984 ◽  
Vol 42 ◽  
pp. 312-313
Author(s):  
C.V.L. Powell
Keyword(s):  
Fine Structure ◽  
Electron Microscope ◽  
Light Intensity ◽  
Scanning Electron Microscope ◽  
Eye Development ◽  
Preliminary Observation ◽  
Columnar Epithelium ◽  
Placopecten Magellanicus ◽  
Environmental Light ◽  
Scanning Electron

The overall fine structure of the eye in Placopecten is similar to that of other scallops. The optic tentacle consists of an outer columnar epithelium which is modified into a pigmented iris and a cornea (Fig. 1). This capsule encloses the cellular lens, retina, reflecting argentea and the pigmented tapetum. The retina is divided into two parts (Fig. 2). The distal retina functions in the detection of movement and the proximal retina monitors environmental light intensity. The purpose of the present study is to describe the ultrastructure of the retina as a preliminary observation on eye development. This is also the first known presentation of scanning electron microscope studies of the eye of the scallop.

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