geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Inositol hexakisphosphate kinase-1 mediates assembly/disassembly of the CRL4-signalosome complex to regulate DNA repair and cell death


, : Inositol hexakisphosphate kinase-1 mediates assembly/disassembly of the CRL4-signalosome complex to regulate DNA repair and cell death. Proceedings of the National Academy of Sciences of the United States of America 111(45): 16005-16010

Inositol polyphosphates containing an energetic pyrophosphate bond are formed primarily by a family of three inositol hexakisphosphate (IP6) kinases (IP6K1-3). The Cullin-RING ubiquitin ligases (CRLs) regulate diverse biological processes through substrate ubiquitylation. CRL4, comprising the scaffold Cullin 4A/B, the E2-interacting Roc1/2, and the adaptor protein damage-specific DNA-binding protein 1, is activated by DNA damage. Basal CRL4 activity is inhibited by binding to the COP9 signalosome (CSN). UV radiation and other stressors dissociate the complex, leading to E3 ligase activation, but signaling events that trigger signalosome dissociation from CRL4 have been unclear. In the present study, we show that, under basal conditions, IP6K1 forms a ternary complex with CSN and CRL4 in which IP6K1 and CRL4 are inactive. UV dissociates IP6K1 to generate IP7, which then dissociates CSN-CRL4 to activate CRL4. Thus, IP6K1 is a novel CRL4 subunit that transduces UV signals to mediate disassembly of the CRL4-CSN complex, thereby regulating nucleotide excision repair and cell death.

US$19.90

PMID: 25349427

DOI: 10.1073/pnas.1417900111


Other references

Sass, B.; Vlahakis, G.; Heston, W.E., 1982: Precursor lesions and pathogenesis of spontaneous mammary tumors in mice. Results are given from a histological study of spontaneous precursor and neoplastic lesions of the mammary gland in inbred and hybrid female mice. The spontaneous tumours described include mammary gland adenocarcinomas with subaceous cell nests, t...

Gai, S.Annie.; Wittrup, K.Dane., 2007: Yeast surface display for protein engineering and characterization. Yeast surface display is being employed to engineer desirable properties into proteins for a broad variety of applications. Labeling with soluble ligands enables rapid and quantitative analysis of yeast-displayed libraries by flow cytometry, while...

Rice-Evans, C.A.; Diplock, A.T., 1993: Current status of antioxidant therapy. There is evidence that free radical damage contributes to the aetiology of many chronic health problems such as emphysema, cardiovascular and inflammatory diseases, cataracts, and cancer. In this review we are not concerned with tissue damage in v...

Trussell, J.C., 2014: Male reproductive endocrinology: when to replace gonadotropins. Infertility is generally defined as a couple's inability to conceive after 1 year of unprotected intercourse. When infertile couples seek assistance, a male factor will be identified half of the time. Once the male has been evaluated, there a...

Colette, C.; Percheron, C.; Pham, C.T.; Boniface, H.; Thomas, N.; Guiter, J.; Monnier, L., 1993: Renal handling of calcium in hypercalciuric calcium oxalate nephrolithiasis. In order to gain further insight into the mechanisms of calcium (Ca) homeostasis in hypercalciuria, we studied 32 lithiasic patients who were divided into three groups: normocalciuric patients (NC; n = 11), patients with absorptive hypercalciuria...

Oettel, M., 2004: The endocrine pharmacology of testosterone therapy in men. The review starts off by outlining the history of the discovery of the male sex hormone testosterone and the historical background to the various, often dubious, approaches to the treatment of age-related endocrine disorders in older men. A discus...

Maschmeyer, G.; Hiddemann, W.; Link, H.; Cornely, O.; Glass, B.; Wilhelm, M.; Helmerking, M.; Adam, D., 1997: Empirical antifungal therapy in febrile neutropenic patients with high-grade hematological malignancies and pulmonary infiltrates or refractory fever of unknown origin. Blood 90(10 SUPPL 1 PART 2): 230B, Nov 15

Kanwar, J.S.; Grewal, J.S., 1966: Direct and residual availability of native and applied potassium in soil. The availability of soil and fertilizer K in Ludhiana soil was studied in pots by growing 3 crops, paddy, wheat and paddy, in succession. Application of K, at the rate of 50, 100 and 200 ppm. K2O/ acre, had a significant direct effect on the 1st c...

Anonymous, 1968: Position statement on confidentiality and privilege with special reference to psychiatric patients. American Journal of Psychiatry 124(7): 1015-1016

Anonymous, 2011: The tradeoff between memory capacity and precision is weaker in recall than in discrimination. The capacity of the visual working memory depends on the precision of the representations. Previously we have shown very limited working memory capacity for detecting changes in the shape (phase structure) of the radial frequency (RF) patterns. We...