04 Fakultät Energie-, Verfahrens- und Biotechnik

Permanent URI for this collectionhttps://elib.uni-stuttgart.de/handle/11682/5

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2015 - 201932020 - 20232

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Institute: search.filters.UBSInstitut.Institut für Zellbiologie und ImmunologieAuthor: search.filters.author.Olayioye, Monilola A.

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Now showing 1 - 5 of 5
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    Golgi screen identifies the RhoGEF Solo as a novel regulator of RhoB and endocytic transport
    (2023) Lungu, Cristiana; Meyer, Florian; Hörning, Marcel; Steudle, Jasmin; Braun, Anja; Noll, Bettina; Benz, David; Fränkle, Felix; Schmid, Simone; Eisler, Stephan A.; Olayioye, Monilola A.
    The control of intracellular membrane trafficking by Rho GTPases is central to cellular homeostasis. How specific guanine nucleotide exchange factors and GTPase‐activating proteins locally balance GTPase activation in this process is nevertheless largely unclear. By performing a microscopy‐based RNAi screen, we here identify the RhoGEF protein Solo as a functional counterplayer of DLC3, a RhoGAP protein with established roles in membrane trafficking. Biochemical, imaging and optogenetics assays further uncover Solo as a novel regulator of endosomal RhoB. Remarkably, we find that Solo and DLC3 control not only the activity, but also total protein levels of RhoB in an antagonistic manner. Together, the results of our study uncover the first functionally connected RhoGAP‐RhoGEF pair at endomembranes, placing Solo and DLC3 at the core of endocytic trafficking.
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    Spatiotemporal control of intracellular membrane trafficking by Rho GTPases
    (2019) Olayioye, Monilola A.; Noll, Bettina; Hausser, Angelika
    As membrane-associated master regulators of cytoskeletal remodeling, Rho GTPases coordinate a wide range of biological processes such as cell adhesion, motility, and polarity. In the last years, Rho GTPases have also been recognized to control intracellular membrane sorting and trafficking steps directly; however, how Rho GTPase signaling is regulated at endomembranes is still poorly understood. In this review, we will specifically address the local Rho GTPase pools coordinating intracellular membrane trafficking with a focus on the endo- and exocytic pathways. We will further highlight the spatiotemporal molecular regulation of Rho signaling at endomembrane sites through Rho regulatory proteins, the GEFs and GAPs. Finally, we will discuss the contribution of dysregulated Rho signaling emanating from endomembranes to the development and progression of cancer.
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    The GEF‐H1/PKD3 signaling pathway promotes the maintenance of triple‐negative breast cancer stem cells
    (2019) Lieb, Wolfgang S.; Lungu, Cristiana; Tamas, Raluca; Berreth, Hannah; Rathert, Philipp; Storz, Peter; Olayioye, Monilola A.; Hausser, Angelika
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    A global microRNA screen identifies regulators of the ErbB receptor signaling network
    (2015) Bischoff, Annabell; Bayerlová, Michaela; Strotbek, Michaela; Schmid, Simone; Beissbarth, Tim; Olayioye, Monilola A.
    Background: The growth factor heregulin (HRG) potently stimulates epithelial cell survival and proliferation through the binding of its cognate receptor ErbB3 (also known as HER3). ErbB3-dependent signal transmission relies on the dimerization partner ErbB2, a receptor tyrosine kinase that is frequently overexpressed and/or amplified in breast cancer cells. Substantial evidence suggests that deregulated ErbB3 expression also contributes to the transformed phenotype of breast cancer cells. Results: By genome-wide screening, we identify 43 microRNAs (miRNAs) that specifically impact HRG-induced activation of the PI3K-Akt pathway. Bioinformatic analysis combined with experimental validation reveals a highly connected molecular miRNA-gene interaction network particularly for the negative screen hits. For selected miRNAs, namely miR-149, miR-148b, miR-326, and miR-520a-3p, we demonstrate the simultaneous downregulation of the ErbB3 receptor and multiple downstream signaling molecules, explaining their efficient dampening of HRG responses and ascribing to these miRNAs potential context-dependent tumor suppressive functions. Conclusions: Given the contribution of HRG signaling and the PI3K-Akt pathway in particular to tumorigenesis, this study not only provides mechanistic insight into the function of miRNAs but also has implications for future clinical applications.
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    Proteasomal turnover of the RhoGAP tumor suppressor DLC1 is regulated by HECTD1 and USP7
    (2022) Frey, Yannick; Franz-Wachtel, Mirita; Macek, Boris; Olayioye, Monilola A.
    The Rho GTPase activating protein Deleted in Liver Cancer 1 (DLC1) is frequently downregulated through genetic and epigenetic mechanisms in various malignancies, leading to aberrant Rho GTPase signaling and thus facilitating cancer progression. Here we show that in breast cancer cells, dysregulation of DLC1 expression occurs at the protein level through rapid degradation via the ubiquitin-proteasome system. Using mass spectrometry, we identify two novel DLC1 interaction partners, the ubiquitin-ligase HECTD1 and the deubiquitinating enzyme ubiquitin-specific-processing protease 7 (USP7). While DLC1 protein expression was rapidly downregulated upon pharmacological inhibition of USP7, siRNA-mediated knockdown of HECTD1 increased DLC1 protein levels and impaired its degradation. Immunofluorescence microscopy analyses revealed that the modulation of HECTD1 levels and USP7 activity altered DLC1 abundance at focal adhesions, its primary site of action. Thus, we propose opposing regulatory mechanisms of DLC1 protein homeostasis by USP7 and HECTD1, which could open up strategies to counteract downregulation and restore DLC1 expression in cancer.