Multiprotein Complexes

Publication Title: 
Nature

The lengths of human telomeres, which protect chromosome ends from degradation and end fusions, are crucial determinants of cell lifespan. During embryogenesis and in cancer, the telomerase enzyme counteracts telomeric DNA shortening. As shown in cancer cells, human telomerase binds the shelterin component TPP1 at telomeres during the S phase of the cell cycle, and adds ~60 nucleotides in a single round of extension, after which telomerase is turned off by unknown mechanisms.

Author(s): 
Chen, Liuh-Yow
Redon, Sophie
Lingner, Joachim
Publication Title: 
Nature

The lengths of human telomeres, which protect chromosome ends from degradation and end fusions, are crucial determinants of cell lifespan. During embryogenesis and in cancer, the telomerase enzyme counteracts telomeric DNA shortening. As shown in cancer cells, human telomerase binds the shelterin component TPP1 at telomeres during the S phase of the cell cycle, and adds ~60 nucleotides in a single round of extension, after which telomerase is turned off by unknown mechanisms.

Author(s): 
Chen, Liuh-Yow
Redon, Sophie
Lingner, Joachim
Publication Title: 
Gerontology

The fungicide rapamycin increases lifespan in eukaryotes by interfering with the activity of a serine/threonine kinase called TOR (target of rapamycin). TOR complex 1 (TORC1) is an essential integrator of cellular nutrient cues, growth signals and cellular metabolism. Here, we review major components of TORC1, its downstream effectors and lifespan studies in various organisms involving these signaling components. In particular, we focus on the role of rapamycin in mitochondrial biogenesis, in metabolic regulation and in the control of reactive oxygen species production.

Author(s): 
Pan, Yong
Nishida, Yuya
Wang, Margaret
Verdin, Eric
Publication Title: 
Biochemical Society Transactions

Autophagy is a catabolic pathway in which the cell sequesters cytoplasmic material, including long-lived proteins, lipids and organelles, in specialized double-membrane vesicles, called autophagosomes. Subsequently, autophagosomes communicate with the lysosomal compartment and acquire acidic hydrolases for final cargo degradation. This process of partial self-eating secures the survival of eukaryotic cells during starvation periods and is critically regulated by mTORC1 (mammalian target of rapamycin complex 1).

Author(s): 
Bakula, Daniela
Takacs, Zsuzsanna
Proikas-Cezanne, Tassula
Publication Title: 
Genes & Development

The Spt-Ada-Gcn5-acetyltransferase (SAGA) chromatin-modifying complex possesses acetyltransferase and deubiquitinase activities. Within this modular complex, Ataxin-7 anchors the deubiquitinase activity to the larger complex. Here we identified and characterized Drosophila Ataxin-7 and found that reduction of Ataxin-7 protein results in loss of components from the SAGA complex.

Author(s): 
Mohan, Ryan D.
Dialynas, George
Weake, Vikki M.
Liu, Jianqi
Martin-Brown, Skylar
Florens, Laurence
Washburn, Michael P.
Workman, Jerry L.
Abmayr, Susan M.
Publication Title: 
Nature

How adult tissue stem and niche cells respond to the nutritional state of an organism is not well understood. Here we find that Paneth cells, a key constituent of the mammalian intestinal stem-cell (ISC) niche, augment stem-cell function in response to calorie restriction. Calorie restriction acts by reducing mechanistic target of rapamycin complex 1 (mTORC1) signalling in Paneth cells, and the ISC-enhancing effects of calorie restriction can be mimicked by rapamycin.

Author(s): 
Yilmaz, ÷mer H.
Katajisto, Pekka
Lamming, Dudley W.
G¸ltekin, Yetis
Bauer-Rowe, Khristian E.
Sengupta, Shomit
Birsoy, Kivanc
Dursun, Abdulmetin
Yilmaz, V. Onur
Selig, Martin
Nielsen, G. Petur
Mino-Kenudson, Mari
Zukerberg, Lawrence R.
Bhan, Atul K.
Deshpande, Vikram
Sabatini, David M.
Publication Title: 
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences

Chronic inhibition of the protein synthesis regulator mTORC1 through rapamycin extends life span in mice, with longer extension in females than in males. Whether rapamycin treatment inhibits protein synthesis or whether it does so differently between sexes has not been examined. UM-HET3 mice were fed a control or rapamycin-supplemented (Rap) diet for 12 weeks. Protein synthesis in mixed, cytosolic (cyto), and mitochondrial (mito) fractions and DNA synthesis and mTORC1 signaling were determined in skeletal muscle, heart, and liver.

Author(s): 
Drake, Joshua C.
Peelor, Frederick F.
Biela, Laurie M.
Watkins, Molly K.
Miller, Richard A.
Hamilton, Karyn L.
Miller, Benjamin F.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Malaria parasites use hemoglobin (Hb) as a major nutrient source in the intraerythrocytic stage, during which heme is converted to hemozoin (Hz). The formation of Hz is essential for parasite survival, but to date, the underlying mechanisms of Hb degradation and Hz formation are poorly understood. We report the presence of a ?200-kDa protein complex in the food vacuole that is required for Hb degradation and Hz formation. This complex contains several parasite proteins, including falcipain 2/2', plasmepsin II, plasmepsin IV, histo aspartic protease, and heme detoxification protein.

Author(s): 
Chugh, Monika
Sundararaman, Vidhya
Kumar, Saravanan
Reddy, Vanga S.
Siddiqui, Waseem A.
Stuart, Kenneth D.
Malhotra, Pawan
Publication Title: 
The American Journal of Pathology

Ubiquitinated endosomal proteins that are deposited into the lumens of multivesicular bodies are either sorted for lysosomal-mediated degradation or secreted as exosomes into the extracellular milieu. The mechanisms that underlie the sorting of cellular cargo proteins are currently unknown. In this study, we show that the COP9 signalosome (CSN)-associated protein CSN5 quantitatively regulated proteins that were sorted into exosomes.

Author(s): 
Liu, Yuelong
Shah, Spandan V.
Xiang, Xiaoyu
Wang, Jianhua
Deng, Zhong-Bin
Liu, Cunren
Zhang, Liming
Wu, Jianming
Edmonds, Tara
Jambor, Christina
Kappes, John C.
Zhang, Huang-Ge
Publication Title: 
PLoS genetics

The molecular chaperone Hsp90 is essential in eukaryotes, in which it facilitates the folding of developmental regulators and signal transduction proteins known as Hsp90 clients. In contrast, Hsp90 is not essential in bacteria, and a broad characterization of its molecular and organismal function is lacking. To enable such characterization, we used a genome-scale phylogenetic analysis to identify genes that co-evolve with bacterial Hsp90.

Author(s): 
Press, Maximilian O.
Li, Hui
Creanza, Nicole
Kramer, Günter
Queitsch, Christine
Sourjik, Victor
Borenstein, Elhanan

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