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H6533

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Shuyang Chen et al.
Nature, 549(7672), 399-403 (2017-09-05)
The melanocortin-1 receptor (MC1R), a G-protein-coupled receptor, has a crucial role in human and mouse pigmentation. Activation of MC1R in melanocytes by α-melanocyte-stimulating hormone (α-MSH) stimulates cAMP signalling and melanin production and enhances DNA repair after ultraviolet irradiation. Individuals carrying...
Kancharana Bala Bhaskara Rao et al.
FEBS letters, 593(16), 2177-2193 (2019-06-19)
Isocitrate dehydrogenases (IDHs) are metabolic enzymes that are mutated in several cancers, resulting in overproduction of d-2-hydroxyglutarate (D-2HG). However, the signalling pathways and factors that regulate mutant IDHs or their metabolites remain elusive. Here, we report that in synchronized cells...
Tami Coursey et al.
Journal of virology, 92(16) (2018-06-08)
Histone posttranslational modifications (PTMs) impart information that regulates chromatin structure and activity. Their effects are mediated by histone reader proteins that bind specific PTMs to modify chromatin and/or recruit appropriate effectors to alter the chromatin landscape. Despite their crucial juxtaposition...
Junji Xing et al.
Nature immunology, 17(12), 1373-1380 (2016-11-01)
The respiratory tract is heavily populated with innate immune cells, but the mechanisms that control such cells are poorly defined. Here we found that the E3 ubiquitin ligase TRIM29 was a selective regulator of the activation of alveolar macrophages, the...
Jing Du et al.
Molecular carcinogenesis, 58(11), 2149-2160 (2019-08-27)
Autophagy is a self-proteolytic process that degrades intracellular material to maintain cellular homeostasis. Transcription factor EB (TFEB) is the master activator that regulates the transcription of genes involved in autophagy and lysosomal biogenesis. However, the cotranscriptional factors of TFEB are...
Kevin C Corbit et al.
The Journal of biological chemistry, 278(15), 13061-13068 (2003-01-29)
Protein kinase C (PKC) regulates activation of the Raf-1 signaling cascade by growth factors, but the mechanism by which this occurs has not been elucidated. Here we report that one mechanism involves dissociation of Raf kinase inhibitory protein (RKIP) from...
Li Huang et al.
Autophagy, 15(3), 407-422 (2018-09-14)
Glucose produced from photosynthesis is a key nutrient signal regulating root meristem activity in plants; however, the underlying mechanisms remain poorly understood. Here, we show that, by modulating reactive oxygen species (ROS) levels, the conserved macroautophagy/autophagy degradation pathway contributes to...
Songlin Liu et al.
Frontiers in pharmacology, 10, 1316-1316 (2019-12-04)
Dysregulation of retinoblastoma (Rb) signaling pathway have been established as a requirement for glioblastoma (GBM) initiation and progression, which suggests that blockade of CDK4/6-Rb signaling axis for GBM treatment. Palbociclib, a selective inhibitor of the cyclin-dependent kinases CDK4/6, has been...
Wan-Chen Hsieh et al.
Nature communications, 9(1), 463-463 (2018-02-02)
X-linked lymphoproliferative syndrome type-2 (XLP-2) is a primary immunodeficiency disease attributed to XIAP mutation and is triggered by infection. Here, we show that mouse Xiap-/- regulatory T (Treg) cells and human XIAP-deficient Treg cells are defective in suppressive function. The...
Cathleen Holze et al.
Nature immunology, 19(2), 130-140 (2017-12-20)
Reactive oxygen species (ROS) are generated by virus-infected cells; however, the physiological importance of ROS generated under these conditions is unclear. Here we found that the inflammation and cell death induced by exposure of mice or cells to sources of...
Alexey Stukalov et al.
Nature, 594(7862), 246-252 (2021-04-13)
The emergence and global spread of SARS-CoV-2 has resulted in the urgent need for an in-depth understanding of molecular functions of viral proteins and their interactions with the host proteome. Several individual omics studies have extended our knowledge of COVID-19...
S Santini et al.
Oncogene, 33(9), 1113-1123 (2013-02-26)
Ataxia Telangiectasia Mutated (ATM) kinase, a central regulator of the DNA damage response, regulates the activity of several E3-ubiquitin ligases, and the ubiquitination-proteasome system is a consistent target of ATM. ITCH is an E3-ubiquitin ligase that modulates the ubiquitination of...
Chae Young Hwang et al.
The Journal of biological chemistry, 285(10), 7827-7837 (2010-01-08)
Tripartite motif (TRIM) protein TRIM5alpha has been shown to restrict human immunodeficiency virus, type 1 infection in Old World monkey cells at the early post-entry step by poorly understood mechanisms. Currently, the physiological function of TRIM5alpha is not known. In...
Ernest C So et al.
The Journal of biological chemistry, 291(11), 5832-5843 (2016-01-13)
Legionella pneumophila, the causative agent of Legionnaire's disease, uses its type IV secretion system to translocate over 300 effector proteins into host cells. These effectors subvert host cell signaling pathways to ensure bacterial proliferation. Despite their importance for pathogenesis, the...
Jannatul Ferdoush et al.
Molecular and cellular biology, 40(7) (2020-01-15)
Although an F-box protein, Mdm30, is found to regulate ubiquitylation of the Sub2 component of TREX (transcription-export) complex for proteasomal degradation in stimulation of mRNA export, it remains unknown whether such ubiquitin-proteasome system (UPS) regulation of Sub2 occurs cotranscriptionally via...
Tsz On Lai et al.
The Journal of general virology, 100(3), 484-496 (2019-01-25)
Human papillomavirus (HPV) infection contributes to virtually all cases of cervical cancer, the fourth most common cancer affecting women worldwide. The oncogenicity of HPV is mainly attributable to the E6 and E7 oncoproteins. HPV-52 is the seventh most common HPV...
Cheuk Yiu Tenny Chung et al.
Biomedicines, 8(10) (2020-10-15)
BRISC and BRCA1-A complex member 2 (Babam2) plays an essential role in promoting cell cycle progression and preventing cellular senescence. Babam2-deficient fibroblasts show proliferation defect and premature senescence compared with their wild-type (WT) counterpart. Pluripotent mouse embryonic stem cells (mESCs)...
Joanna F McGouran et al.
Chemistry & biology, 20(12), 1447-1455 (2013-12-03)
Posttranslational modification with ubiquitin (Ub) controls many cellular processes, and aberrant ubiquitination can contribute to cancer, immunopathology, and neurodegeneration. The versatility arises from the ability of Ub to form polymer chains with eight distinct linkages via lysine side chains and...
Ao Zhang et al.
EMBO reports, 21(7), e49666-e49666 (2020-05-01)
Inflammasomes are intracellular complexes that form in the cytosol of inflammatory cells. NLRP3 is one of the sensor proteins in the complex that can recognize a wide variety of stimuli ranging from microbial components to environmental particulates. Here, we report...
Mathivanan Jothi et al.
Cell cycle (Georgetown, Tex.), 11(5), 895-908 (2012-02-16)
The chimeric PAX3-FKHR transcription factor is present in a majority of alveolar rhabdomyosarcoma (ARMS), an aggressive skeletal muscle cancer of childhood. PAX3-FKHR-mediated aberrant myogenic gene expression resulting in escape from terminal differentiation program is believed to contribute in ARMS development....
Manuele Rebsamen et al.
Nature, 519(7544), 477-481 (2015-01-07)
Cell growth and proliferation are tightly linked to nutrient availability. The mechanistic target of rapamycin complex 1 (mTORC1) integrates the presence of growth factors, energy levels, glucose and amino acids to modulate metabolic status and cellular responses. mTORC1 is activated...
Xi Wu et al.
The Journal of cell biology, 217(1), 139-149 (2017-11-16)
Mitochondria are double-membraned organelles playing essential metabolic and signaling functions. The mitochondrial proteome is under surveillance by two proteolysis systems: the ubiquitin-proteasome system degrades mitochondrial outer-membrane (MOM) proteins, and the AAA proteases maintain the proteostasis of intramitochondrial compartments. We previously...
Matthew A B Baker et al.
Nature structural & molecular biology, 23(3), 197-203 (2016-02-09)
Large protein complexes assemble spontaneously, yet their subunits do not prematurely form unwanted aggregates. This paradox is epitomized in the bacterial flagellar motor, a sophisticated rotary motor and sensory switch consisting of hundreds of subunits. Here we demonstrate that Escherichia...
Kaloyan M Tsanov et al.
Nature cell biology, 19(1), 60-67 (2016-12-20)
Signalling and post-transcriptional gene control are both critical for the regulation of pluripotency, yet how they are integrated to influence cell identity remains poorly understood. LIN28 (also known as LIN28A), a highly conserved RNA-binding protein, has emerged as a central...
Cecilia Domínguez Conde et al.
The Journal of clinical investigation, 129(10), 4194-4206 (2019-08-27)
Polymerase δ is essential for eukaryotic genome duplication and synthesizes DNA at both the leading and lagging strands. The polymerase δ complex is a heterotetramer comprising the catalytic subunit POLD1 and the accessory subunits POLD2, POLD3, and POLD4. Beyond DNA...
A Fauster et al.
Cell death & disease, 6, e1767-e1767 (2015-05-23)
Necroptosis is a form of regulated necrotic cell death mediated by receptor-interacting serine/threonine-protein kinase 1 (RIPK1) and RIPK3. Necroptotic cell death contributes to the pathophysiology of several disorders involving tissue damage, including myocardial infarction, stroke and ischemia-reperfusion injury. However, no...
Justin M Reitsma et al.
Cell, 171(6), 1326-1339 (2017-11-07)
SCF (Skp1-Cullin-F-box) ubiquitin ligases comprise several dozen modular enzymes that have diverse roles in biological regulation. SCF enzymes share a common catalytic core containing Cul1⋅Rbx1, which is directed toward different substrates by a variable substrate receptor (SR) module comprising 1...
David S Hewings et al.
Nature communications, 9(1), 1162-1162 (2018-03-23)
Activity-based probes (ABPs) are widely used to monitor the activity of enzyme families in biological systems. Inferring enzyme activity from probe reactivity requires that the probe reacts with the enzyme at its active site; however, probe-labeling sites are rarely verified....
Qian Wang et al.
Nature communications, 11(1), 679-679 (2020-02-06)
Auxin determines the developmental fate of plant tissues, and local auxin concentration is precisely controlled. The role of auxin transport in modulating local auxin concentration has been widely studied but the regulation of local auxin biosynthesis is less well understood....
Katharina L Willmann et al.
Nature communications, 5, 5360-5360 (2014-11-20)
Primary immunodeficiency disorders enable identification of genes with crucial roles in the human immune system. Here we study patients suffering from recurrent bacterial, viral and Cryptosporidium infections, and identify a biallelic mutation in the MAP3K14 gene encoding NIK (NF-κB-inducing kinase)....
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