Damage-specific DNA binding protein 1 (DDB1): a protein with a wide range of functions

Iovine, Barbara; Iannella, Maria Luigia; Bevilacqua, Maria Assunta

doi:10.1016/j.biocel.2011.09.001

Cited by 91 publications

(74 citation statements)

References 28 publications

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“…The RNA helicase DDX3X, and the DNA helicases Pontin and Reptin, are also components of the INO80 complex (Huen et al, 2010; Vella et al, 2012), of histone deacetylase (Gallant, 2007) and β-catenin (Bauer et al, 2000; Kim et al, 2005; Sierra et al, 2006) complexes. DDB1 is the core component of the Cul4 ubiquitin ligase complex participating in DNA damage-activated chromatin modification (Higa et al, 2006; Iovine et al, 2011). Finally, DBC1 is an inhibitor of the histone deacetylases Sirt1 (Zhao et al, 2008) and HDAC3 (Chini et al, 2010).…”

Section: Resultsmentioning

confidence: 99%

The TRPM7 Chanzyme Is Cleaved to Release a Chromatin-Modifying Kinase

Krapivinsky

Manasian

et al. 2014

Cell

153

131

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SUMMARY TRPM7 is a ubiquitous ion channel and kinase, a unique ‘chanzyme’, required for proper early embryonic development. It conducts Zn2+, Mg2+, Ca2+ as well as monovalent cations, and contains a functional serine/threonine kinase at its carboxyl terminus. Here, we show that in normal tissues and cell lines, the kinase is proteolytically cleaved from the channel domain in a cell type-specific manner. These TRPM7 Cleaved Kinase fragments (M7CKs) translocate to the nucleus and bind multiple components of chromatin remodeling complexes, including Polycomb group proteins. In the nucleus, the kinase phosphorylates specific serines/threonines of histones. M7CK-dependent phosphorylation of H3Ser10 at promoters of TRPM7-dependent genes correlates with their activity. We also demonstrate that cytosolic free [Zn2+] is TRPM7-dependent and regulates M7CK binding to transcription factors containing zinc-finger domains. These findings suggest that TRPM7-mediated modulation of intracellular Zn2+ concentration couples ion channel signaling to epigenetic chromatin covalent modifications that affect gene expression patterns.

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Section: Resultsmentioning

confidence: 99%

The TRPM7 Chanzyme Is Cleaved to Release a Chromatin-Modifying Kinase

Krapivinsky

Manasian

et al. 2014

Cell

153

131

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“…His tag pulldown assay was performed as previously described [18]. Cells transfected with plasmids were incubated with 20 lM MG132 for 4 h before lysed in HUBA (His-ubiquitin buffer A: 6 M guanidine-HCl, 0.1 M Na 2 HPO 4 /NaH 2 PO 4 , 10 mM imidazole, pH8.0).…”

Section: His Tag Pulldown Assaymentioning

confidence: 99%

HBx affects CUL4–DDB1 function in both positive and negative manners

Guo

Wang

Ren

et al. 2014

Biochemical and Biophysical Research Communications

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“…DDB1 (DNA-damage–binding protein 1) is a scaffolding component of the DDB1-CUL4A ubiquitin E3 ligase complex (20–22). Within this complex, DDB1 serves as the linker protein between CUL4A and substrate-binding proteins (21,23).…”

Section: Introductionmentioning

confidence: 99%

DDB1-Mediated CRY1 Degradation Promotes FOXO1-Driven Gluconeogenesis in Liver

et al. 2017

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Targeted protein degradation through ubiquitination is an important step in the regulation of glucose metabolism. Here, we present evidence that the DDB1-CUL4A ubiquitin E3 ligase functions as a novel metabolic regulator that promotes FOXO1-driven hepatic gluconeogenesis. In vivo, hepatocyte-specific Ddb1 deletion leads to impaired hepatic gluconeogenesis in the mouse liver but protects mice from high-fat diet–induced hyperglycemia. Lack of Ddb1 downregulates FOXO1 protein expression and impairs FOXO1-driven gluconeogenic response. Mechanistically, we discovered that DDB1 enhances FOXO1 protein stability via degrading the circadian protein cryptochrome 1 (CRY1), a known target of DDB1 E3 ligase. In the Cry1 depletion condition, insulin fails to reduce the nuclear FOXO1 abundance and suppress gluconeogenic gene expression. Chronic depletion of Cry1 in the mouse liver not only increases FOXO1 protein but also enhances hepatic gluconeogenesis. Thus, we have identified the DDB1-mediated CRY1 degradation as an important target of insulin action on glucose homeostasis.

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Damage-specific DNA binding protein 1 (DDB1): a protein with a wide range of functions

Cited by 91 publications

References 28 publications

The TRPM7 Chanzyme Is Cleaved to Release a Chromatin-Modifying Kinase

The TRPM7 Chanzyme Is Cleaved to Release a Chromatin-Modifying Kinase

HBx affects CUL4–DDB1 function in both positive and negative manners

DDB1-Mediated CRY1 Degradation Promotes FOXO1-Driven Gluconeogenesis in Liver

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