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- Cadigan Lab: SOX9 and TCF transcription factors associate to mediate Wnt/β-catenin target gene activation in colorectal cancer
- DeSantis/Nandakumar Labs: KASH5 protein
- Jakob Lab: From guide to guard—activation mechanism of the stress-sensing chaperone Get3
- Wang Lab: GRASP55 regulates the unconventional secretion and aggregation of mutant huntingtin
- Chapman Lab: Mechanistic insights into accelerated α-synuclein aggregation mediated by human microbiome-associated functional amyloids
Cadigan Lab: SOX9 and TCF transcription factors associate to mediate Wnt/β-catenin target gene activation in colorectal cancer
Aravinda-Bharathi Ramakrishnan, Peter E. Burby, Kavya Adiga, Ken M. Cadigan
Abstract: Activation of the Wnt/β-catenin pathway regulates gene expression by promoting the formation of a β-catenin–T-cell factor (TCF) complex on target enhancers. In addition to TCFs, other transcription factors interact with the Wnt/β-catenin pathway at different levels to produce tissue-specific patterns of Wnt target gene expression. The transcription factor SOX9 potently represses many Wnt target genes by downregulating β-catenin protein levels. Here, we find using colony formation and cell growth assays that SOX9 surprisingly promotes the proliferation of Wnt-driven...
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DeSantis/Nandakumar Labs: The KASH5 protein involved in meiotic chromosomal movements is a novel dynein activating adaptor
Ritvija Agrawal, John P Gillies, Juliana L Zang, Jingjing Zhang, Sharon R Garrott, Hiroki Shibuya, Jayakrishnan Nandakumar, Morgan E DeSantis
Dynein harnesses ATP hydrolysis to move cargo on microtubules in multiple biological contexts. Dynein meets a unique challenge in meiosis by moving chromosomes tethered to the nuclear envelope to facilitate homolog pairing essential for gametogenesis. Though processive dynein motility requires binding to an activating adaptor, the identity of the activating adaptor required for dynein to move meiotic chromosomes is unknown. We show that the meiosis-specific nuclear-envelope protein KASH5 is a dynein activating adaptor: KASH5 directly binds dynein using a mechanism conserved...
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Wang Lab: GRASP55 regulates the unconventional secretion and aggregation of mutant huntingtin
Erpan Ahat, Sarah Bui, Jianchao Zhang, Felipe da Veiga Leprevost, Lisa Sharkey, Whitney Reid, Alexey I. Nesvizhskii, Henry L. Paulson, Yanzhuang Wang,
Abstract: Recent studies demonstrated that the Golgi reassembly stacking proteins (GRASPs), especially GRASP55, regulate Golgi-independent unconventional secretion of certain cytosolic and transmembrane cargoes; however, the underlying mechanism remains unknown. Here, we surveyed several neurodegenerative disease–related proteins, including mutant huntingtin (Htt-Q74), superoxide dismutase 1 (SOD1), tau, and TAR DNA–binding protein 43 (TDP-43), for unconventional secretion; our results show that Htt-Q74 is most robustly secreted in a GRASP55-dependent manner. Using Htt-Q74...
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Jakob Lab: From guide to guard—activation mechanism of the stress-sensing chaperone Get3
Kathrin Ulrich, Ákos Farkas, Olivia Chan, Olivia Katamanin, Blanche Schwappach, Ursula Jakob
SUMMARY:
Oxidative stress conditions can cause ATP depletion, oxidative protein unfolding, and potentially toxic protein aggregation. To alleviate this proteotoxic stress, the highly conserved yeast protein, Get3, switches from its guiding function as an ATP-dependent targeting factor for tail-anchored proteins to its guarding function as an ATP-independent molecular chaperone that prevents irreversible protein aggregation. Here, we demonstrate that activation of Get3’s chaperone function follows a tightly orchestrated multi-step process, centered around...
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