Biomedical subjects

Ashim Mukherjee

Publications and source records attributed to Ashim Mukherjee.

4 recordsLinked to original sources

PubMed2006

Maternal expression and function of the Drosophila sox gene Dichaete during oogenesis.

Members of the Sox family of DNA-binding HMG domain proteins have been shown to regulate gene transcription in a wide range of developmental processes, including sex determination, neurogenesis, and chondrogenesis. However, little is known about their potential functions in developing germline tissues. In Drosophila, the Sox protein Dichaete (a.k.a., Fish-hook) is a member of the SoxB subgroup whose HMG domain shares strong sequence similarity to that of vertebrate Sox2. Dichaete exhibits dynamic expression in embryonic and larval stages and has pleiotropic functions in a variety of tissues. In this study, we extend analyses of Dichaete function and show that expression of Dichaete protein is detected in the developing oocyte during early to mid stages of oogenesis. Strikingly, Dichaete exhibits cytoplasmic distribution and is not detected in the oocyte nucleus. Germline mosaic analyses revealed that the Dichaete gene has maternal functions that influence dorsal/ventral patterning of the egg chamber. Dichaete mutant eggs exhibit defects in formation of the dorsal appendages, differentiation of dorsal/anterior follicle cells, and mislocalization of Gurken protein and gurken mRNA. Dichaete protein was shown to possess RNA-binding capabilities, suggesting a direct post-transcriptional role in regulating RNA functions.

Animals↗

PubMed2005

Regulation of Notch signalling by non-visual beta-arrestin.

Signalling activity of the Notch receptor, which plays a fundamental role in metazoan cell fate determination, is controlled at multiple levels. We uncovered a Notch signal-controlling mechanism that depends on the ability of the non-visual beta-arrestin, Kurtz (Krz), to influence the degradation and, consequently, the function of the Notch receptor. We identified Krz as a binding partner of a known Notch-pathway modulator, Deltex (Dx), and demonstrated the existence of a trimeric Notch-Dx-Krz protein complex. This complex mediates the degradation of the Notch receptor through a ubiquitination-dependent pathway. Our results establish a novel mode of regulation of Notch signalling and define a new function for non-visual beta-arrestins.

Animals↗

PubMed2005

Protein interaction mapping: a Drosophila case study.

The Drosophila (fruit fly) model system has been instrumental in our current understanding of human biology, development, and diseases. Here, we used a high-throughput yeast two-hybrid (Y2H)-based technology to screen 102 bait proteins from Drosophila melanogaster, most of them orthologous to human cancer-related and/or signaling proteins, against high-complexity fly cDNA libraries. More than 2300 protein-protein interactions (PPI) were identified, of which 710 are of high confidence. The computation of a reliability score for each protein-protein interaction and the systematic identification of the interacting domain combined with a prediction of structural/functional motifs allow the elaboration of known complexes and the identification of new ones. The full data set can be visualized using a graphical Web interface, the PIMRider (http://pim.hybrigenics.com), and is also accessible in the PSI standard Molecular Interaction data format. Our fly Protein Interaction Map (PIM) is surprisingly different from the one recently proposed by Giot et al. with little overlap between the two data sets. Analysis of the differences in data sets and methods suggests alternative strategies to enhance the accuracy and comprehensiveness of the post-genomic generation of broad-scale protein interaction maps.

Animals↗

PubMed2004

The Drosophila F box protein archipelago regulates dMyc protein levels in vivo.

BACKGROUND: The Myc oncoprotein is an important regulator of cellular growth in metazoan organisms. Its levels and activity are tightly controlled in vivo by a variety of mechanisms. In normal cells, Myc protein is rapidly degraded, but the mechanism of its degradation is not well understood. RESULTS: Here we present genetic and biochemical evidence that Archipelago (Ago), the F box component of an SCF-ubiquitin ligase and the Drosophila ortholog of a human tumor suppressor, negatively regulates the levels and activity of Drosophila Myc (dMyc) protein in vivo. Mutations in archipelago (ago) result in strongly elevated dMyc protein levels and increased tissue growth. Genetic interactions indicate that ago antagonizes dMyc function during development. Archipelago binds dMyc and regulates its stability, and the ability of Ago to bind dMyc in vitro correlates with its ability to inhibit dMyc accumulation in vivo. CONCLUSIONS: Our data indicate that archipelago is an important inhibitor of dMyc in developing tissues. Because archipelago can also regulate Cyclin E levels and Notch activity, these results indicate how a single F box protein can be responsible for the degradation of key components of multiple pathways that control growth and cell cycle progression.

Amino Acid Sequence↗