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Ilenia Segatto et al.
Molecular oncology, 8(3), 766-780 (2014-03-26)
In early breast cancer, local relapses represent a determinant and not simply an indicator of risk for distant relapse and death. Notably, 90% of local recurrences occur at or close to the same quadrant of the primary cancer. Relevance of
Anders Esberg et al.
PloS one, 6(6), e20829-e20829 (2011-06-23)
Iwr1, a protein conserved throughout eukaryotes, was originally identified by its physical interaction with RNA polymerase (Pol) II. Here, we identify Iwr1 in a genetic screen designed to uncover proteins involved in Pol III transcription in S. cerevisiae. Iwr1 is
Iivo Hetemäki et al.
Science immunology, 6(65), eabe3454-eabe3454 (2021-11-27)
The Ikaros family transcription factors regulate lymphocyte development. Loss-of-function variants in IKZF1 cause primary immunodeficiency, but Ikaros family members IKZF2 and IKZF3 have not yet been associated with immunodeficiency. Here, we describe a pedigree with a heterozygous truncating variant in
Xiao-Bin Lv et al.
Oncotarget, 6(34), 36370-36382 (2015-10-16)
Dysregulation of SOX10 was reported to be correlated with the progression of multiple cancer types, including melanocytic tumors and tumors of the nervous system. However, the mechanisms by which SOX10 is dysregulated in these tumors are poorly understood. In this
Min Mo et al.
Proceedings of the National Academy of Sciences of the United States of America, 106(46), 19527-19532 (2009-11-06)
The anaphase-promoting complex (APC), or cyclosome, is a ubiquitin ligase with major roles in cell cycle regulation. It is required for mitotic exit, but must be deactivated for the G(1)/S phase transition to occur. APC consists of at least 12
Anisyah Ridiandries et al.
International journal of molecular sciences, 18(1) (2017-01-19)
Angiogenesis is involved in the inflammation and proliferation stages of wound healing, to bring inflammatory cells to the wound and provide a microvascular network to maintain new tissue formation. An excess of inflammation, however, leads to prolonged wound healing and
Toru Suzuki et al.
RNA biology, 19(1), 234-246 (2022-02-08)
CCR4-NOT complex-mediated mRNA deadenylation serves critical functions in multiple biological processes, yet how this activity is regulated is not fully understood. Here, we show that osmotic stress induces MAPKAPK-2 (MK2)-mediated phosphorylation of CNOT2. Programmed cell death is greatly enhanced by
Priya Kapoor-Vazirani et al.
Nature communications, 13(1), 6707-6707 (2022-11-08)
Sterile alpha motif and HD domain-containing protein 1 (SAMHD1) has a dNTPase-independent function in promoting DNA end resection to facilitate DNA double-strand break (DSB) repair by homologous recombination (HR); however, it is not known if upstream signaling events govern this
Victoria N Jordan et al.
Chembiochem : a European journal of chemical biology, 24(16), e202300108-e202300108 (2023-05-11)
Controlled protein degradation by the ubiquitin-proteasome pathway is critical for almost all cellular processes. E3 ubiquitin ligases are responsible for targeting proteins for ubiquitylation and subsequent proteasomal degradation with spatial and temporal precision. While studies have revealed various E3-substrate pairs
Prashant K Mishra et al.
Molecular biology of the cell, 30(8), 1020-1036 (2019-02-07)
Evolutionarily conserved polo-like kinase, Cdc5 (Plk1 in humans), associates with kinetochores during mitosis; however, the role of cell cycle-dependent centromeric ( CEN) association of Cdc5 and its substrates that exclusively localize to the kinetochore have not been characterized. Here we
PamelaSara E Head et al.
The Journal of biological chemistry, 292(24), 9919-9931 (2017-05-04)
Sirtuin 2 (SIRT2) is a sirtuin family deacetylase, which maintains genome integrity and prevents tumorigenesis. Although Sirt2 deficiency in mice leads to tumorigenesis, the functional significance of somatic SIRT2 mutations in human tumors is unclear. Using structural insight combined with
Jonas D Albarnaz et al.
Nature microbiology, 7(1), 154-168 (2021-12-25)
Infection of mammalian cells with viruses activates NF-κB to induce the expression of cytokines and chemokines and initiate an antiviral response. Here, we show that a vaccinia virus protein mimics the transactivation domain of the p65 subunit of NF-κB to
Yang Gao et al.
Nature cell biology, 22(9), 1064-1075 (2020-08-26)
Immunotherapies that target programmed cell death protein 1 (PD-1) and its ligand PD-L1 as well as cytotoxic T-lymphocyte-associated protein 4 (CTLA4) have shown impressive clinical outcomes for multiple tumours. However, only a subset of patients achieves durable responses, suggesting that
Jacob R Manjarrez et al.
PloS one, 9(3), e90054-e90054 (2014-03-13)
The expression of the wild-type tumor-suppressor gene DBC2 (Deleted-in-Breast Cancer 2, a.k.a RhoBTB2) is suppressed in many cancers, in addition to breast cancer. In a screen for Cdc37-associated proteins, DBC2 was identified to be a potential client protein of the
Mariia Levchenko et al.
PloS one, 11(12), e0168518-e0168518 (2016-12-20)
The outer mitochondrial membrane protein Atg32 is the central receptor for mitophagy, the mitochondria-specific form of autophagy. Atg32 is an unstable protein, and is rapidly degraded under conditions in which mitophagy is not induced. Here we show that Atg32 undergoes
Dongqin Chen et al.
Nature communications, 8(1), 2265-2265 (2017-12-24)
In addition to acting as a cellular energy source, ATP can also act as a damage-associated molecular pattern in both animals and plants. Stomata are leaf pores that control gas exchange and, therefore, impact critical functions such as photosynthesis, drought
Boda Zhou et al.
Arteriosclerosis, thrombosis, and vascular biology, 31(11), 2676-2684 (2011-08-13)
Vascular smooth muscle cell (SMC) proliferation has an indispensable role in the pathogenesis of vascular disease, but the mechanism is not fully elucidated. The epigenetic enzyme histone deacetylase 7 (HDAC7) is involved in endothelial homeostasis and SMC differentiation and could
Lihi Gur-Arie et al.
The Journal of biological chemistry, 295(28), 9409-9420 (2020-05-15)
Microbial pathogens often target the host mitogen-activated protein kinase (MAPK) network to suppress host immune responses. We previously identified a bacterial type III secretion system effector, termed NleD, a metalloprotease that inactivates MAPKs by specifically cleaving their activation loop. Here
Gabrielle Vieyres et al.
PLoS pathogens, 16(6), e1008554-e1008554 (2020-06-17)
Lipid droplets are essential cellular organelles for storage of fatty acids and triglycerides. The hepatitis C virus (HCV) translocates several of its proteins onto their surface and uses them for production of infectious progeny. We recently reported that the lipid
Sam Strickson et al.
Proceedings of the National Academy of Sciences of the United States of America, 114(17), E3481-E3489 (2017-04-14)
It is widely accepted that the essential role of TRAF6 in vivo is to generate the Lys63-linked ubiquitin (K63-Ub) chains needed to activate the "master" protein kinase TAK1. Here, we report that TRAF6 E3 ligase activity contributes to but is
Xiaoyu Zhang et al.
Nature chemical biology, 15(7), 737-746 (2019-06-19)
Ligand-dependent protein degradation has emerged as a compelling strategy to pharmacologically control the protein content of cells. So far, however, only a limited number of E3 ligases have been found to support this process. Here, we use a chemical proteomic
Hope A Cole et al.
Nucleic acids research, 42(20), 12512-12522 (2014-10-29)
Eukaryotic chromatin is composed of nucleosomes, which contain nearly two coils of DNA wrapped around a central histone octamer. The octamer contains an H3-H4 tetramer and two H2A-H2B dimers. Gene activation is associated with chromatin disruption: a wider nucleosome-depleted region
Yeyun Ouyang et al.
eLife, 13 (2024-01-22)
Mitochondrial membrane potential directly powers many critical functions of mitochondria, including ATP production, mitochondrial protein import, and metabolite transport. Its loss is a cardinal feature of aging and mitochondrial diseases, and cells closely monitor membrane potential as an indicator of
Luca Puzzi et al.
Cell cycle (Georgetown, Tex.), 14(1), 64-73 (2014-12-09)
To date, a complete understanding of the molecular events leading to DNA replication origin activation in mammalian cells still remains elusive. In this work, we report the results of a high resolution chromatin immunoprecipitation study to detect proteins interacting with
Sebastian Alers et al.
Autophagy, 7(12), 1423-1433 (2011-10-26)
Under normal growth conditions the mammalian target of rapamycin complex 1 (mTORC1) negatively regulates the central autophagy regulator complex consisting of Unc-51-like kinases 1/2 (Ulk1/2), focal adhesion kinase family-interacting protein of 200 kDa (FIP200) and Atg13. Upon starvation, mTORC1-mediated repression
Jen-Wei Huang et al.
Nature communications, 11(1), 2948-2948 (2020-06-13)
Homologous recombination (HR) mediates the error-free repair of DNA double-strand breaks to maintain genomic stability. Here we characterize C17orf53/MCM8IP, an OB-fold containing protein that binds ssDNA, as a DNA repair factor involved in HR. MCM8IP-deficient cells exhibit HR defects, especially
Lin-Chun Chang et al.
Nucleic acids research, 40(3), 1331-1344 (2011-10-15)
The yeast RNA helicase Dhh1p has been shown to associate with components of mRNA decay and is involved in mRNA decapping and degradation. An RNA-binding protein, Rbp1p, is known to bind to the 3'-UTR of porin (POR1) mRNA, and induces
John K Barrows et al.
Nucleic acids research, 49(6), 3263-3273 (2021-03-05)
The tumor suppressor BRCA1 is considered a master regulator of genome integrity. Although widely recognized for its DNA repair functions, BRCA1 has also been implicated in various mechanisms of chromatin remodeling and transcription regulation. However, the precise role that BRCA1
Jessica Laiman et al.
The Journal of cell biology, 222(2) (2022-11-30)
Insulin-stimulated translocation of glucose transporter 4 (GLUT4) to plasma membrane of skeletal muscle is critical for postprandial glucose uptake; however, whether the internalization of GLUT4 is also regulated by insulin signaling remains unclear. Here, we discover that the activity of
Wei-Chung Chiang et al.
Cell, 148(1-2), 322-334 (2012-01-24)
Extended longevity is often correlated with increased resistance against various stressors. Insulin/IGF-1-like signaling (IIS) is known to have a conserved role in aging and cellular mechanisms against stress. In C. elegans, genetic studies suggest that heat-shock transcription factor HSF-1 is required
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