The ZZ domain as a new epigenetic reader and a degradation signal sensor

Zhang, Yi; Mi, Wenyi; Xue, Yongming; Shi, Xiaobing; Kutateladze, Tatiana G.

doi:10.1080/10409238.2018.1564730

Cited by 19 publications

(15 citation statements)

References 79 publications

(108 reference statements)

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“…Both SQST-1 and the human ortholog, SQSTM1/p62, have been shown to bind to and target ubiquitinated proteins to an organelle (sequestosome) for subsequent degradation by autophagy [ 81 , 82 ]. The ZZ-domain, particularly the zinc-coordinating Cys-X2-Cys residues, has been shown to be essential for this process [ 83 , 84 ]. Additionally, sqst-3 is expressed in response to exogenous cadmium [ 85 ], suggesting that the sequestosome-related family might be involved in divalent cation metal stress responses.…”

Section: Discussionmentioning

confidence: 99%

Natural variation in the sequestosome-related gene, sqst-5, underlies zinc homeostasis in Caenorhabditis elegans

et al. 2020

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Zinc is an essential trace element that acts as a co-factor for many enzymes and transcription factors required for cellular growth and development. Altering intracellular zinc levels can produce dramatic effects ranging from cell proliferation to cell death. To avoid such fates, cells have evolved mechanisms to handle both an excess and a deficiency of zinc. Zinc homeostasis is largely maintained via zinc transporters, permeable channels, and other zinc-binding proteins. Variation in these proteins might affect their ability to interact with zinc, leading to either increased sensitivity or resistance to natural zinc fluctuations in the environment. We can leverage the power of the roundworm nematode Caenorhabditis elegans as a tractable metazoan model for quantitative genetics to identify genes that could underlie variation in responses to zinc. We found that the laboratory-adapted strain (N2) is resistant and a natural isolate from Hawaii (CB4856) is sensitive to micromolar amounts of exogenous zinc supplementation. Using a panel of recombinant inbred lines, we identified two large-effect quantitative trait loci (QTL) on the left arm of chromosome III and the center of chromosome V that are associated with zinc responses. We validated and refined both QTL using near-isogenic lines (NILs) and identified a naturally occurring deletion in sqst-5, a sequestosome-related gene, that is associated with resistance to high exogenous zinc. We found that this deletion is relatively common across strains within the species and that variation in sqst-5 is associated with zinc resistance. Our results offer a possible mechanism for how organisms can respond to naturally high levels of zinc in the environment and how zinc homeostasis varies among individuals.

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Section: Discussionmentioning

confidence: 99%

Natural variation in the sequestosome-related gene, sqst-5, underlies zinc homeostasis in Caenorhabditis elegans

et al. 2020

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“…The nonhydrogen atoms were checked for the average RMSD to reach 0.3 Å with the help of minimization through the OPLS-AA force field. 40 , 41 …”

Section: Methodsmentioning

confidence: 99%

Interpretations on the Interaction between Protein Tyrosine Phosphatase and E7 Oncoproteins of High and Low-Risk HPV: A Computational Perception

Aarthy

2021

ACS Omega

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The most prevalent and common sexually transmitted infection is caused by human papillomavirus (HPV) among sexually active women. Numerous genotypes of HPV are available, among which the major oncoproteins E6 and E7 lead to the progression of cervical cancer. The E7 oncoprotein interacts with cytoplasmic tumor suppressor protein PTPN14, which is the key regulator of cellular growth control pathways effecting the reduction of steady-state level. Disrupting the interaction between the tumor suppressor and the oncoprotein is vital to cease the development of cancer. Hence, the mechanism of interaction between E7 and tumor suppressor is explored through protein–protein and protein–ligand binding along with the conformational stability studies. The obtained results state that the LXCXE domain of HPV E7 of high and low risks binds with the tumor suppressor protein. Also, the small molecules bind in the interface of E7–PTPN14 that disrupts the interaction between the tumor suppressor and oncoprotein. These results were further supported by the dynamics simulation stating the stability over the bounded complex and the energy maintained during postdocking as well as postdynamics calculations. These observations possess an avenue in the drug discovery that leads to further validation and also proposes a potent drug candidate to treat cervical cancer caused by HPV.

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“…Recent structural work reveals the molecular explanation. Ada2 contains the SANT histone-binding domain (found in Swi3, ADA2, N-Cor, and TFIIIB, hence named SANT) (Sterner et al 2002), a ZZtype zinc finger (ZZ) domain involved in histone tail binding (Zhang et al 2019) and a Swi3p, Rsc8p, and Moira (SWIRM) domain, a eukaryotic domain found in proteins implicated in chromatin remodeling and gene expression (Boyer et al 2002;Sterner et al 2002;Qian et al 2005;Da et al 2006). The SANT domain does not appear to act as a histone tail-binding module, because it is positioned away from the Gcn5 peptide-binding pocket.…”

Section: The Composition Of the Hat Module Facilitates Its Functionmentioning

confidence: 99%

The SAGA chromatin-modifying complex: the sum of its parts is greater than the whole

Soffers

Workman

2020

Genes Dev.

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There are many large protein complexes involved in transcription in a chromatin context. However, recent studies on the SAGA coactivator complex are generating new paradigms for how the components of these complexes function, both independently and in concert. This review highlights the initial discovery of the canonical SAGA complex 23 years ago, our evolving understanding of its modular structure and the relevance of its modular nature for its coactivator function in gene regulation.

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The ZZ domain as a new epigenetic reader and a degradation signal sensor

Cited by 19 publications

References 79 publications

Natural variation in the sequestosome-related gene, sqst-5, underlies zinc homeostasis in Caenorhabditis elegans

Natural variation in the sequestosome-related gene, sqst-5, underlies zinc homeostasis in Caenorhabditis elegans

Interpretations on the Interaction between Protein Tyrosine Phosphatase and E7 Oncoproteins of High and Low-Risk HPV: A Computational Perception

The SAGA chromatin-modifying complex: the sum of its parts is greater than the whole

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