Affiner les résultats

Langue

Université de Fribourg

Cyclin-dependent kinase 5 (CDK5) regulates the circadian clock

Brenna, Andrea ; Olejniczak, Iwona ; Chavan, Rohit ; Ripperger, Jürgen A ; Langmesser, Sonja ; Cameroni, Elisabetta ; Hu, Zehan ; De Virgilio, Claudio ; Dengjel, Jörn ; Albrecht, Urs

In: eLife, 2019, vol. 8, p. e50925

Circadian oscillations emerge from transcriptional and post-translational feedback loops. An important step in generating rhythmicity is the translocation of clock components into the nucleus, which is regulated in many cases by kinases. In mammals, the kinase promoting the nuclear import of the key clock component Period 2 (PER2) is unknown. Here, we show that the cyclin-dependent kinase 5...

Université de Fribourg

Myosin 1b regulates nuclear AKT activation by preventing localization of PTEN in the nucleus

Yu, Yi ; Xiong, Yuyan ; Ladeiras, Diogo ; Yang, Zhihong ; Ming, Xiu-Fen

In: iScience, 2019, vol. 19, p. 39–53

Insulin-induced AKT activation is dependent on phosphoinositide 3-kinase and opposed by tumor suppressor phosphatase and tensin homolog (PTEN). Our previous study demonstrates that myosin 1b (MYO1B) mediates arginase-II-induced activation of mechanistic target of rapamycin complex 1 that is regulated by AKT. However, the role of MYO1B in AKT activation is unknown. Here we show that silencing...

Università della Svizzera italiana

SHP-2 in lymphocytes’ cytokine and inhibitory receptor signaling

Niogret, Charlène ; Birchmeier, Walter ; Guarda, Greta

In: Frontiers in immunology, 2019, vol. 10, no. 2468, p. 1-11

Somewhat counterintuitively, the tyrosine phosphatase SHP-2 (SH2 domain- containing protein tyrosine phosphatase-2) is crucial for the activation of extracellular signal-regulated kinase (ERK) downstream of various growth factor receptors, thereby exerting essential developmental functions. This phosphatase also deploys proto-oncogenic functions and specific inhibitors have recently been ...

Université de Fribourg

Regulation of TRPM8 channel activity by Src-mediated tyrosine phosphorylation

Manolache, Alexandra ; Selescu, Tudor ; Maier, G. Larisa ; Mentel, Mihaela ; Ionescu, Aura Elena ; Neacsu, Cristian ; Babes, Alexandru ; Szedlacsek, Stefan Eugen

In: Journal of Cellular Physiology, 2019, p. -

The transient receptor potential melastatin type 8 (TRPM8) receptor channel is expressed in primary afferent neurons where it is the main transducer of innocuous cold temperatures and also in a variety of tumors, where it is involved in progression and metastasis. Modulation of this channel by intracellular signaling pathways has therefore important clinical implications. We investigated the...

Université de Fribourg

Phosphorylation of mitochondrial matrix proteins regulates their selective mitophagic degradation

Kolitsida, Panagiota ; Zhou, Jianwen ; Rackiewicz, Michal ; Nolic, Vladimir ; Dengjel, Jörn ; Abeliovich, Hagai

In: Proceedings of the National Academy of Sciences, 2019, vol. 116, no. 41, p. 20517–20527

Mitophagy is an important quality-control mechanism in eukaryotic cells, and defects in mitophagy correlate with aging phenomena and neurodegenerative disorders. It is known that different mitochondrial matrix proteins undergo mitophagy with very different rates but, to date, the mechanism underlying this selectivity at the individual protein level has remained obscure. We now present...

Université de Fribourg

Multilayered control of protein turnover by torc1 and atg1

Hu, Zehan ; Raucci, Serena ; Jaquenoud, Malika ; Hatakeyama, Riko ; Stumpe, Michael ; Rohr, Rudolf ; Reggiori, Fulvio ; Virgilio, Claudio De ; Dengjel, Jörn

In: Cell Reports, 2019, vol. 28, no. 13, p. 3486-3496.e6

The target of rapamycin complex 1 (TORC1) is a master regulator of cell homeostasis, which promotes anabolic reactions and synchronously inhibits catabolic processes such as autophagy-mediated protein degradation. Its prime autophagy target is Atg13, a subunit of the Atg1 kinase complex that acts as the gatekeeper of canonical autophagy. To study whether the activities of TORC1 and Atg1 are...

Università della Svizzera italiana

Epigenetic and transcriptional control of mast cell responses

Monticelli, Silvia ; Leoni

In: F1000 research, 2017, vol. 6, p. 2064

Mast cells are tissue-resident, innate immune cells present in most tissues of the body and are important effector and immunomodulatory cells. Differentiated mast cells typically are characterized by the surface expression of the receptors KIT and FcεRI, the latter especially being important for stimulation through IgE antibodies, although these cells have the ability to respond to a wide...

Università della Svizzera italiana

Conformational occlusion of blockade antibody epitopes, a novel mechanism of GII.4 human norovirus immune evasion

Lindesmith, Lisa C. ; Mallory, Michael L. ; Debbink, Kari ; Donaldson, Eric F. ; Brewer-Jensen, Paul D. ; Swann, Excel W. ; Sheahan, Timothy P. ; Graham, Rachel L. ; Beltramello, Martina ; Corti, Davide ; Lanzavecchia, Antonio ; Baric, Ralph S.

In: mSphere, 2018, vol. 3, no. 1, p. e00518-17

Extensive antigenic diversity within the GII.4 genotype of human norovirus is a major driver of pandemic emergence and a significant obstacle to development of cross- protective immunity after natural infection and vaccination. However, human and mouse monoclonal antibody studies indicate that, although rare, antibodies to conserved GII.4 blockade epitopes are generated. The mechanisms by...

Università della Svizzera italiana

The atypical receptor CCRL2 (C-C Chemokine Receptor-Like 2) does not act as a decoy receptor in endothelial cells

Mazzotti, Chiara ; Gagliostro, Vincenzo ; Bosisio, Daniela ; Del Prete, Annalisa ; Tiberio, Laura ; Thelen, Marcus ; Sozzani, Silvano

In: Frontiers in immunology, 2017, vol. 8, p. 1233

C-C chemokine receptor-like 2 (CCRL2) is a non-signaling seven-transmembrane domain (7-TMD) receptor related to the atypical chemokine receptor (ACKR) family. ACKRs bind chemokines but do not activate G protein-dependent signaling or cell functions. ACKRs were shown to regulate immune functions in vivo by their ability to scavenge chemokines from the local environment. This study was ...

Università della Svizzera italiana

Epithelial-mesenchymal transition in cancer metastasis through the lymphatic syste

Karlsson, Mikael C. ; Gonzalez, Santiago F. ; Welin, Josefin ; Fuxe, Jonas

In: Molecular oncology, 2017, vol. 11, p. 781–791

It was already in the 18th century when the French surgeon LeDran first noted that breast cancer patients with spread of tumor cells to their axillary lymph nodes had a drastically worse prognosis than patients without spread (LeDran et al., ). Since then, metastatic spread of cancer cells to regional lymph nodes has been established as the most important prognostic factor in many types of...