Dataset Information

The tumor suppressor SCRIB is a negative modulator of the Wnt/-catenin signaling (part 2)

ABSTRACT: Epithelial tissues are highly organized structures that rely on cell polarity pathways driven by membrane receptors and scaffolding proteins. SCRIBBLE is a cytoplasmic scaffold present at cell-cell junctions in polarized cells that contains LRR and PDZ domains. The current interactome of SCRIB and LRRC1 consists of 67 and 30 protein interaction partners respectively with only 9 (10%) common partners (BioGRID, version 3.5). Our study identified a protein complex associated to SCRIB stabilized by the inhibition of the proteasome and further characterize SCRIB act as negative modulator of the Wnt/β-catenin signaling.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hek-293t Cell

SUBMITTER: Luc Camoin

LAB HEAD: Camoin Luc

PROVIDER: PXD013636 | Pride | 2019-09-25

REPOSITORIES: Pride

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Publications

The Tumor Suppressor SCRIB is a Negative Modulator of the Wnt/β-Catenin Signaling Pathway.

Daulat Avais M AM Wagner Mônica Silveira MS Walton Alexandra A Baudelet Emilie E Audebert Stéphane S Camoin Luc L Borg Jean-Paul JP

Proteomics 20191020 21-22

SCRIB is a scaffold protein containing leucine-rich repeats (LRR) and PSD-95/Dlg-A/ZO-1 domains (PDZ) that localizes at the basolateral membranes of polarized epithelial cells. Deregulation of its expression or localization leads to epithelial defects and tumorigenesis in part as a consequence of its repressive role on several signaling pathways including AKT, ERK, and HIPPO. In the present work, a proteomic approach is used to characterize the protein complexes associated to SCRIB and its paral ...[more]

PMID: 31513346

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Project description:Current human reproductive risk assessment methods rely on semen and serum hormone analyses, which are not easily comparable to the histopathological endpoints and mating studies used in animal testing. Because of these limitations, there is a need to develop universal evaluations that reliably reflect male reproductive function. We hypothesized that toxicant-induced testicular injury can be detected in sperm using mRNA transcripts as indicators of insult. To test this, we exposed adult male Fischer 344 rats to low doses of model testicular toxicants and classically characterized the testicular injury while simultaneously evaluating sperm mRNA transcripts from the same animals. Overall, this study aimed to: 1) identify sperm transcripts altered after exposure to the model testicular toxicant, 2,5-hexanedione (HD) using microarrays; 2) expand on the HD-induced transcript changes in a comprehensive time course experiment using qRT-PCR arrays; and 3) test these injury indicators after exposure to another model testicular toxicant, carbendazim (CBZ). Microarray analysis of HD-treated adult Fischer 344 rats identified 128 altered sperm mRNA transcripts when compared to control using linear models of microarray analysis (q < 0.05). All transcript alterations disappeared after 3 months of post-exposure recovery. In the time course experiment, time-dependent alterations were observed for 12 candidate transcripts selected from the microarray data based upon fold change and biological relevance, and 8 of these transcripts remained significantly altered after the 3-month recovery period (p < 0.05). In the last experiment, 8 candidate transcripts changed after exposure to CBZ (p < 0.05). The two testicular toxicants produced distinct molecular signatures with only 4 overlapping transcripts between them, each occurring in opposite directions. Overall, these results suggest that sperm mRNA transcripts are indicators of low dose toxicant-induced testicular injury in the rat. Rats were exposed to sub-chronic low doses of the Sertoli cell toxicant 2,5-hexanedione (HD) or water (control for HD) for 3 months. Some rats in each group underwent 3 months of post-exposure recovery.

Dataset Information

The tumor suppressor SCRIB is a negative modulator of the Wnt/-catenin signaling (part 2)

Publications

The Tumor Suppressor SCRIB is a Negative Modulator of the Wnt/β-Catenin Signaling Pathway.

Similar Datasets

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