Proteolysis

Publication Title: 
Journal of Ethnopharmacology

ETHNOPHARMACOLOGICAL RELEVANCE: Eucommia ulmoides Oliv. Bark. (EUE), has commonly been used to fortify the muscles and lungs, lower blood pressure, prevent miscarriage, improve the tone of liver and kidneys, and promote longevity the traditional tonic medicines of Korea, China, and Japan. AIM OF THE STUDY: In this study, we investigated that the neuroprotective activities and possible mechanisms of EUE aqueous extract in hydrogen peroxide (H(2)O(2))-induced neuronal cell death in human SH-SY5Y neuroblastoma cells.

Author(s): 
Kwon, Seung-Hwan
Kim, Min-Jung
Ma, Shi-Xun
You, In-Jee
Hwang, Ji-Young
Oh, Ji-Hwan
Kim, Sun-Yeou
Kim, Hyoung-Chun
Lee, Seok-Yong
Jang, Choon-Gon
Publication Title: 
Nature Chemical Biology

In polyglutamine (polyQ) diseases, only certain neurons die, despite widespread expression of the offending protein. PolyQ expansion may induce neurodegeneration by impairing proteostasis, but protein aggregation and toxicity tend to confound conventional measurements of protein stability. Here, we used optical pulse labeling to measure effects of polyQ expansions on the mean lifetime of a fragment of huntingtin, the protein that causes Huntington's disease, in living neurons.

Author(s): 
Tsvetkov, Andrey S.
Arrasate, Montserrat
Barmada, Sami
Ando, D. Michael
Sharma, Punita
Shaby, Benjamin A.
Finkbeiner, Steven
Publication Title: 
Biochimica Et Biophysica Acta

Botulinum neurotoxins (BoNTs) are proteins of great interest not only because of their extreme toxicity but also paradoxically for their therapeutic applications. All the known serotypes (A-G) have varying degrees of longevity and potency inside the neuronal cell. Differential chemical modifications such as phosphorylation and ubiquitination have been suggested as possible mechanisms for their longevity, but the molecular basis of the longevity remains unclear.

Author(s): 
Kumar, Raj
Kukreja, Roshan V.
Cai, Shuowei
Singh, Bal R.
Publication Title: 
Developmental Cell

Developmental timing genes catalyze stem cell progression and animal maturation programs across taxa. Caenorhabditis elegans DRE-1/FBXO11 functions in an SCF E3-ubiquitin ligase complex to regulate the transition to adult programs, but its cognate proteolytic substrates are unknown. Here, we identify the conserved transcription factor BLMP-1 as a substrate of the SCF(DRE-1/FBXO11) complex. blmp-1 deletion suppressed dre-1 mutant phenotypes and exhibited developmental timing defects opposite to dre-1.

Author(s): 
Horn, Moritz
Geisen, Christoph
Cermak, Lukas
Becker, Ben
Nakamura, Shuhei
Klein, Corinna
Pagano, Michele
Antebi, Adam
Publication Title: 
Aging Cell

Nutrient availability influences an organism's life history with profound effects on metabolism and lifespan. The association between a healthy lifespan and metabolism is incompletely understood, but a central factor is glucose metabolism. Although glucose is an important cellular energy source, glucose restriction is associated with extended lifespan in simple animals and a reduced incidence of age-dependent pathologies in humans. We report here that glucose enrichment delays mutant polyglutamine, TDP-43, FUS, and amyloid-?

Author(s): 
Tauffenberger, Arnaud
Vaccaro, Alexandra
Aulas, Anais
Vande Velde, Christine
Parker, J. Alex
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

The human malaria parasite Plasmodium falciparum is auxotrophic for most amino acids. Its amino acid needs are met largely through the degradation of host erythrocyte hemoglobin; however the parasite must acquire isoleucine exogenously, because this amino acid is not present in adult human hemoglobin. We report that when isoleucine is withdrawn from the culture medium of intraerythrocytic P. falciparum, the parasite slows its metabolism and progresses through its developmental cycle at a reduced rate.

Author(s): 
Babbitt, Shalon E.
Altenhofen, Lindsey
Cobbold, Simon A.
Istvan, Eva S.
Fennell, Clare
Doerig, Christian
Llinás, Manuel
Goldberg, Daniel E.
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: 
Cell Death & Disease

Withania somnifera or Ashwagandha is a medicinal herb of Ayurveda. Though the extract and purified molecules, withanolides, from this plant have been shown to have different pharmacological activities, their effect on bone formation has not been studied. Here, we show that one of the withanolide, withaferin A (WFA) acts as a proteasomal inhibitor (PI) and binds to specific catalytic β subunit of the 20S proteasome. It exerts positive effect on osteoblast by increasing osteoblast proliferation and differentiation.

Author(s): 
Khedgikar, V.
Kushwaha, P.
Gautam, J.
Verma, A.
Changkija, B.
Kumar, A.
Sharma, S.
Nagar, G. K.
Singh, D.
Trivedi, P. K.
Sangwan, N. S.
Mishra, P. R.
Trivedi, R.
Publication Title: 
Cell Death & Disease

Withania somnifera or Ashwagandha is a medicinal herb of Ayurveda. Though the extract and purified molecules, withanolides, from this plant have been shown to have different pharmacological activities, their effect on bone formation has not been studied. Here, we show that one of the withanolide, withaferin A (WFA) acts as a proteasomal inhibitor (PI) and binds to specific catalytic β subunit of the 20S proteasome. It exerts positive effect on osteoblast by increasing osteoblast proliferation and differentiation.

Author(s): 
Khedgikar, V.
Kushwaha, P.
Gautam, J.
Verma, A.
Changkija, B.
Kumar, A.
Sharma, S.
Nagar, G. K.
Singh, D.
Trivedi, P. K.
Sangwan, N. S.
Mishra, P. R.
Trivedi, R.
Publication Title: 
The Plant Cell

Plant phototropism is an adaptive response to changes in light direction, quantity, and quality that results in optimization of photosynthetic light harvesting, as well as water and nutrient acquisition. Though several components of the phototropic signal response pathway have been identified in recent years, including the blue light (BL) receptors phototropin1 (phot1) and phot2, much remains unknown. Here, we show that the phot1-interacting protein NONPHOTOTROPIC HYPOCOTYL3 (NPH3) functions as a substrate adapter in a CULLIN3-based E3 ubiquitin ligase, CRL3(NPH3).

Author(s): 
Roberts, Diana
Pedmale, Ullas V.
Morrow, Johanna
Sachdev, Shrikesh
Lechner, Esther
Tang, Xiaobo
Zheng, Ning
Hannink, Mark
Genschik, Pascal
Liscum, Emmanuel

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