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Literature summary for 2.7.4.21 extracted from

  • Rao, F.; Xu, J.; Khan, A.B.; Gadalla, M.M.; Cha, J.Y.; Xu, R.; Tyagi, R.; Dang, Y.; Chakraborty, A.; Snyder, S.H.
    Inositol hexakisphosphate kinase-1 mediates assembly/disassembly of the CRL4-signalosome complex to regulate DNA repair and cell death (2014), Proc. Natl. Acad. Sci. USA, 111, 16005-16010.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.7.4.21

Cloned(Commentary)

Cloned (Comment) Organism
gene IP6K1, recombinant expression of GST-tagged enzyme in Escherichia coli strain BL21(DE3), coexpression of IP6K1 prevents enhancement of ubiquitylation by the expression of DDB1/Cul4A in HEK293 cells. IP6K1 expression of shRNA-resistant mouse IP6K1 in IP6K1 knockdown cells, overexpression of TAP-IP6K1 in HEK-293 cells Mus musculus

Inhibitors

Inhibitors Comment Organism Structure
additional information radiation virtually abolishes binding of wild-type IP6K1 to the signalosome Mus musculus
N2-(m-(trifluoromethy)lbenzyl)N6-(p-nitrobenzyl)purine potent and selective inhibitor Mus musculus

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Mus musculus

Organism

Organism UniProt Comment Textmining
Mus musculus Q6PD10 gene IP6K1
-

Synonyms

Synonyms Comment Organism
inositol hexakisphosphate kinase-1
-
 Mus musculus
IP6K1
-
 Mus musculus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
 assay at Mus musculus

Cofactor

Cofactor Comment Organism Structure
ATP
-
 Mus musculus

Expression

Organism Comment Expression
Mus musculus IP6K1 knockdown in MEF cells additional information

General Information

General Information Comment Organism
malfunction the UV-induced CRL4-mediated CDT1 degradation is substantially more rapid in IP6K1-deleted murine embryonic fibroblasts, MEFs, indicating enhanced CRL4 activity in the absence of IP6K1. CRL4-CSN binding is stimulated more by kinase-dead than wild-type IP6K1. IP6K1 knockdown greatly diminishes CRL4-CSN binding, an effect rescued by expressing shRNA-resistant mouse IP6K1 in IP6K1 knockdown cells. IP6K1 depletion augments Cul4A neddylation. The binding of substrate receptor DDB2 to Cul4A is diminished upon IP6K1 depletion Mus musculus
physiological function inositol pyrophosphates containing seven (IP7) or more phosphate groups on a myo-inositol ring are synthesized from inositol hexakisphosphate (IP6) primarily by a family of IP6 kinases. Inositol hexakisphosphate kinase-1 mediates assembly/disassembly of the CRL4-signalosome complex. Under basal conditions, IP6K1 forms a ternary complexwith CSN and CRL4 in which IP6K1 and CRL4 are inactive. UV dissociates IP6K1 to generate IP7, which then dissociates CSN-CRL4 to activate CRL4. IP6K1 is a CRL4 subunit that transduces UV signals to mediate disassembly of the CRL4-CSN complex, thereby regulating nucleotide excision repair and cell death. IP6K1 directly binds to DDB1 and inhibits CRL4. IP6K1 inhibits CRL4 substrate, e.g. c-Jun, ubiquitylation and degradation. CDT1 ubiquitylation is markedly enhanced by overexpressing DDB1/Cul4A, an effect abolished in the presence of IP6K1. CRL4-CSN binding is stimulated more by kinase-dead than wild-type IP6K1 Mus musculus