查看更多>>摘要：? 2022 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.Transcription factor EB (TFEB) belongs to the microphthalmia family of bHLH-leucine zipper transcription factors and was first identified as an oncogene in a subset of renal cell carcinomas. In addition to exhibiting oncogenic activity, TFEB coordinates genetic programs connected with the cellular response to stress conditions, including roles in lysosome biogenesis, autophagy, and modulation of metabolism. As is the case for other transcription factors, the activities of TFEB are not limited to a specific cellular condition such as the response to stress, and recent findings indicate that TFEB has more widespread functions. Here, we review the emerging roles of TFEB in regulating cellular proliferation and motility. The well-established and emerging roles of TFEB suggest that this protein serves as a hub of signaling networks involved in many non-communicable diseases, such as cancer, ischaemic diseases and immune disorders, drug resistance mechanisms, and tissue generation.
查看更多>>摘要：? 2022 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.Nuclear factor erythroid-derived 2-like 2 (NRF2) is a master transcription factor that coordinately regulates the expression of many cytoprotective genes and plays a central role in defense mechanisms against oxidative and electrophilic insults. Although increased NRF2 activity is principally beneficial for our health, NRF2 activation in cancer cells is detrimental. Many human cancers exhibit persistent NRF2 activation and such cancer cells rely on NRF2 for most of their malignant characteristics, such as therapeutic resistance and aggressive tumourigenesis, and thus fall into NRF2 addiction. The persistent activation of NRF2 confers great advantages on cancer cells, whereas it is not tolerated by normal cells, suggesting that certain requirements are necessary for a cell to exploit NRF2 and evolve into malignant cancer cells. In this review, recent reports and data on the genetic, metabolic and immunological features of NRF2-activated cancer cells are summarized, and prerequisites for NRF2 addiction in cancer cells and their therapeutic applications are discussed.
查看更多>>摘要：? 2022 Federation of European Biochemical Societies.Wood frog (Rana sylvatica) freeze tolerance necessitates metabolic rate depression, where costly processes such as gene transcription are commonly suppressed. Epigenetic mechanisms, such as histone lysine methylation, have recently been implicated in hypometabolic states of various animals, although they are underreported in nervous tissues. In the present study, we track the expression of eight lysine methyltransferases, as well as the activity on, and abundance of putative histone products across the freeze–thaw cycle and freeze-associated substresses (anoxia, dehydration) of wood frog brains. Our results suggest that hypomethylation of transcriptionally repressive H3K9 may be a key facet of metabolic recovery during the thawing of nervous tissue, which we speculate may have a positive effect on global gene transcription. Some nonhistone roles for lysine methylation are also proposed.
查看更多>>摘要：? 2022 Federation of European Biochemical Societies.The bZIP transcription factor Atf1 is a key player in the transcriptional programme of Schizosaccharomyces pombe cell cycle. It also controls both expression and degradation of mitotic cyclin Cdc13. Temporal regulation of these opposing functions of Atf1 is critical for fidelity of cell division. Our investigations revealed that an increase in the activity of mitogen-activated protein kinase (MAPK) Spc1 during mitotic exit and the consequent phosphorylation of Atf1 along with the prevailing high activity of cyclin-dependent kinase Cdc2 regulate Cdc13 degradation. Our results also indicate the possibility of a complex interplay between Cdc2 inhibitory kinase Wee1, the anaphase-promoting complex and Atf1 during mitotic exit. These observations provide evidence of new regulatory mechanisms of mitotic exit.
查看更多>>摘要：? 2022 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.To enable chromosomal replication, DNA is unwound by the ATPase molecular motor replicative helicase. The bacterial helicase DnaB is a ring-shaped homo-hexamer whose conformational dynamics are being studied through its different 3D structural states adopted along its functional cycle. Our findings describe a new crystal structure for the apo-DnaB from Vibrio cholerae, forming a planar hexamer with pseudo-symmetry, constituted by a trimer of dimers in which the C-terminal domains delimit a triskelion-shaped hole. This hexamer is labile and inactive. We suggest that it represents an intermediate state allowing the formation of the active NTP-bound hexamer from dimers.
查看更多>>摘要：? 2022 Federation of European Biochemical Societies.DNA replication stress is characterized by impaired replication fork progression, causing some of the replication forks to collapse and form DNA breaks. It is a primary cause of genomic instability leading to oncogenic transformation. The repair-independent functions of the proteins RAD51 and BRCA2, which are involved in homologous recombination (HR)-mediated DNA repair, are crucial for protecting nascent DNA strands from nuclease-mediated degradation. The BRCA2 and CDKN1A-interacting protein (BCCIP) associates with BRCA2 and RAD51 during HR-mediated DNA repair. Here, we investigated the role of BCCIP during the replication stress response. We find that in the presence of replication stress, BCCIP deficiency increases replication fork stalling and results in DNA double-strand break formation. We show that BCCIP is recruited to stalled replication forks and prevents MRE11 nuclease-mediated degradation of nascent DNA strands.
查看更多>>摘要：? 2022 Federation of European Biochemical Societies.p27Kip1 functions to coordinate cell cycle progression through the inhibition of cyclin-dependent kinase (CDK) complexes. p27Kip1 also exerts distinct activities beyond CDK-inhibition, including functioning as a transcriptional regulator. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor with diverse biological roles. The regulatory inputs that control AhR-mediated transcriptional responses are an active area of investigation. AhR was previously established as a direct regulator of p27Kip1 transcription. Here, we report the physical interaction of AhR and p27Kip1 and show that p27Kip1 expression negatively regulates AhR-mediated transcription. p27Kip1 knockout cells display increased AhR nuclear localisation and significantly higher expression of AhR target genes. This work thus identifies new regulatory cross-talk between p27Kip1 and AhR.
查看更多>>摘要：? 2022 Federation of European Biochemical Societies.Casein micelles are extracellular polydisperse assemblies of unstructured casein proteins. Caseins are the major component of milk. Within casein micelles, casein molecules are stabilised by binding to calcium phosphate nanoclusters and, by acting as molecular chaperones, through multivalent interactions. In the light of such interactions, we discuss whether casein micelles can be considered as extracellular condensates formed by liquid–liquid phase separation. We analyse the sequence, structure and interactions of caseins in comparison with proteins forming intracellular condensates. Furthermore, we review the similarities between caseins and small heat-shock proteins whose chaperone activity is linked to phase separation of proteins. By bringing these observations together, we describe a regulatory mechanism for protein condensates, as exemplified by casein micelles.
查看更多>>摘要：? 2022 Federation of European Biochemical Societies.https://doi.org/10.1002/1873-3468.12720 The above article, published online on 22 June 2017 in Wiley Online Library (https://doi.org/10.1002/1873-3468.12720), has been retracted by agreement between the authors, the journal Editor in Chief, Michael Brunner, and John Wiley and Sons Ltd. The retraction has been agreed due to concerns raised regarding the appearance of Fig.?3A and 3B. Fig.?3A shows duplications in the subpanels, while some Fig.?3B subpanels appear to be digitally manipulated. The raw data provided by the authors upon request are not compelling and appear to contain further irregularities. As a result, the data and the conclusions are considered unreliable.
NSTL
Wiley