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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''Tribbles homolog 3''' is a [[protein]] that in humans is encoded by the ''TRIB3'' [[gene]].<ref name="pmid12791994">{{cite journal |vauthors=Du K, Herzig S, Kulkarni RN, Montminy M | title = TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver | journal = Science | volume = 300 | issue = 5625 | pages = 1574–7 |date=Jun 2003 | pmid = 12791994 | pmc =  | doi = 10.1126/science.1079817 }}</ref><ref name="pmid16715410">{{cite journal |vauthors=Hegedus Z, Czibula A, Kiss-Toth E | title = Tribbles: novel regulators of cell function; evolutionary aspects | journal = Cell Mol Life Sci | volume = 63 | issue = 14 | pages = 1632–41 |date=Aug 2006 | pmid = 16715410 | pmc =  | doi = 10.1007/s00018-006-6007-9 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: TRIB3 tribbles homolog 3 (Drosophila)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=57761| accessdate = }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = Tribbles homolog 3 (Drosophila)
| HGNCid = 16228
| Symbol = TRIB3
| AltSymbols =; TRB3; C20orf97; NIPK; SINK; SKIP3
| OMIM = 607898
| ECnumber = 
| Homologene = 10902
| MGIid = 1345675
| GeneAtlas_image1 = PBB_GE_TRIB3_218145_at_tn.png
| Function = {{GNF_GO|id=GO:0003714 |text = transcription corepressor activity}} {{GNF_GO|id=GO:0004672 |text = protein kinase activity}} {{GNF_GO|id=GO:0004860 |text = protein kinase inhibitor activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0005524 |text = ATP binding}} {{GNF_GO|id=GO:0019901 |text = protein kinase binding}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}}
| Process = {{GNF_GO|id=GO:0006350 |text = transcription}} {{GNF_GO|id=GO:0006355 |text = regulation of transcription, DNA-dependent}} {{GNF_GO|id=GO:0006468 |text = protein amino acid phosphorylation}} {{GNF_GO|id=GO:0006469 |text = negative regulation of protein kinase activity}} {{GNF_GO|id=GO:0006915 |text = apoptosis}} {{GNF_GO|id=GO:0043405 |text = regulation of MAPK activity}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 57761
    | Hs_Ensembl = ENSG00000101255
    | Hs_RefseqProtein = NP_066981
    | Hs_RefseqmRNA = NM_021158
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 20
    | Hs_GenLoc_start = 309273
    | Hs_GenLoc_end = 326205
    | Hs_Uniprot = Q96RU7
    | Mm_EntrezGene = 228775
    | Mm_Ensembl = ENSMUSG00000032715
    | Mm_RefseqmRNA = NM_144554
    | Mm_RefseqProtein = NP_653137
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 2
    | Mm_GenLoc_start = 152029648
    | Mm_GenLoc_end = 152034768
    | Mm_Uniprot = Q8K4K2
  }}
}}
'''Tribbles homolog 3 (Drosophila)''', also known as '''TRIB3''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: TRIB3 tribbles homolog 3 (Drosophila)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=57761| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
The protein encoded by this gene is a putative [[protein kinase]] that is induced by the transcription factor [[NF-kappaB]]. It is a [[pseudoenzyme]] that is thought to be a negative regulator of NF-kappaB, and can also sensitize cells to [[TNF]]- and [[TRAIL]]-induced [[apoptosis]]. In addition, this protein has been reported to negatively regulate the cell survival serine-threonine kinase [[AKT1]].<ref name="entrez" /> TRIB3 has recently been associated with neuronal signalling, and like [[TRIB1]] and [[TRIB2]], could be considered as a potential allosteric drug target <ref name="pmid27908682">{{cite journal |vauthors= Eyers PA, Keeshan K, Kannan N | title = Tribbles in the 21st Century: The Evolving Roles of Tribbles Pseudokinases in Biology and Disease. | journal = Trends in Cell Biology | volume = In Press | issue = 9 | pages = S0962-8924(16)30178-7 | year = 2016 | pmid = 27908682 | doi = 10.1016/j.tcb.2016.11.002| pmc=5382568}}</ref><ref name="pmid26517930">{{cite journal |vauthors= Foulkes DM, Byrne DP, Eyers PA | title = Tribbles pseudokinases: novel targets for chemical biology and drug discovery? | journal = Biochemical Society Transactions | volume = 43 | issue = 5 | pages = 1095–1103 | year = 2015 | pmid = 26517930 | doi = 10.1042/BST20150109| url = }}</ref>
{{PBB_Summary
 
| section_title =
==Interactions==
| summary_text = The protein encoded by this gene is a putative protein kinase that is induced by the transcription factor NF-kappaB. The encoded protein is a negative regulator of NF-kappaB and can also sensitize cells to TNF- and TRAIL-induced apoptosis. In addition, this protein can negatively regulate the cell survival serine-threonine kinase AKT1.<ref name="entrez">{{cite web | title = Entrez Gene: TRIB3 tribbles homolog 3 (Drosophila)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=57761| accessdate = }}</ref>
TRIB3 has been shown to [[Protein-protein interaction|interact]] with:
}}
* [[AKT1]],<ref name="pmid12791994" />
* [[CSNK2B]],<ref name="pmid18276110">{{cite journal |vauthors=Zhou Y, Li L, Liu Q, Xing G, Kuai X, Sun J, Yin X, Wang J, Zhang L, He F | title = E3 ubiquitin ligase SIAH1 mediates ubiquitination and degradation of TRB3 | journal = Cell. Signal. | volume = 20 | issue = 5 | pages = 942–8 |date=May 2008 | pmid = 18276110 | doi = 10.1016/j.cellsig.2008.01.010 }}</ref>
* [[Fibronectin]]<ref name=pmid18276110/>
* [[MCM3AP]],<ref name="pmid12743605">{{cite journal |vauthors=Bowers AJ, Scully S, Boylan JF | title = SKIP3, a novel Drosophila tribbles ortholog, is overexpressed in human tumors and is regulated by hypoxia | journal = Oncogene | volume = 22 | issue = 18 | pages = 2823–35 |date=May 2003 | pmid = 12743605 | doi = 10.1038/sj.onc.1206367 }}</ref>
* [[RELA]],<ref name="pmid12736262">{{cite journal |vauthors=Wu M, Xu LG, Zhai Z, Shu HB | title = SINK is a p65-interacting negative regulator of NF-kappaB-dependent transcription | journal = J. Biol. Chem. | volume = 278 | issue = 29 | pages = 27072–9 |date=July 2003 | pmid = 12736262 | doi = 10.1074/jbc.M209814200 }}</ref>
* [[SIAH1]],<ref name=pmid18276110/> and
* [[TIAF1]].<ref name=pmid18276110/>


==References==
==References==
{{reflist|2}}
{{reflist}}
 
==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
*{{cite journal  |vauthors=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1–2 |pages= 171–4 |year= 1994 |pmid= 8125298 |doi=10.1016/0378-1119(94)90802-}}
| citations =
*{{cite journal   |vauthors=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1–2 |pages= 149–56 |year= 1997 |pmid= 9373149 |doi=10.1016/S0378-1119(97)00411-3 }}
*{{cite journal  | author=Hegedus Z, Czibula A, Kiss-Toth E |title=Tribbles: novel regulators of cell function; evolutionary aspects. |journal=Cell. Mol. Life Sci. |volume=63 |issue= 14 |pages= 1632-41 |year= 2006 |pmid= 16715410 |doi= 10.1007/s00018-006-6007-9 }}
*{{cite journal   |vauthors=Deloukas P, Matthews LH, Ashurst J, etal |title=The DNA sequence and comparative analysis of human chromosome 20. |journal=Nature |volume=414 |issue= 6866 |pages= 865–71 |year= 2002 |pmid= 11780052 |doi= 10.1038/414865a }}
*{{cite journal | author=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171-4 |year= 1994 |pmid= 8125298 |doi=  }}
*{{cite journal   |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899  | pmc=139241 }}
*{{cite journal | author=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, ''et al.'' |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1-2 |pages= 149-56 |year= 1997 |pmid= 9373149 |doi= }}
*{{cite journal  |vauthors=Wu M, Xu LG, Zhai Z, Shu HB |title=SINK is a p65-interacting negative regulator of NF-kappaB-dependent transcription. |journal=J. Biol. Chem. |volume=278 |issue= 29 |pages= 27072–9 |year= 2003 |pmid= 12736262 |doi= 10.1074/jbc.M209814200 }}
*{{cite journal | author=Deloukas P, Matthews LH, Ashurst J, ''et al.'' |title=The DNA sequence and comparative analysis of human chromosome 20. |journal=Nature |volume=414 |issue= 6866 |pages= 865-71 |year= 2002 |pmid= 11780052 |doi= 10.1038/414865a }}
*{{cite journal  |vauthors=Bowers AJ, Scully S, Boylan JF |title=SKIP3, a novel Drosophila tribbles ortholog, is overexpressed in human tumors and is regulated by hypoxia. |journal=Oncogene |volume=22 |issue= 18 |pages= 2823–35 |year= 2003 |pmid= 12743605 |doi= 10.1038/sj.onc.1206367 }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal   |vauthors=Huang J, Teng L, Liu T, etal |title=Identification of a novel serine/threonine kinase that inhibits TNF-induced NF-kappaB activation and p53-induced transcription. |journal=Biochem. Biophys. Res. Commun. |volume=309 |issue= 4 |pages= 774–8 |year= 2003 |pmid= 13679039 |doi=10.1016/j.bbrc.2003.08.069  }}
*{{cite journal  | author=Wu M, Xu LG, Zhai Z, Shu HB |title=SINK is a p65-interacting negative regulator of NF-kappaB-dependent transcription. |journal=J. Biol. Chem. |volume=278 |issue= 29 |pages= 27072-9 |year= 2003 |pmid= 12736262 |doi= 10.1074/jbc.M209814200 }}
*{{cite journal   |vauthors=Ota T, Suzuki Y, Nishikawa T, etal |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal | author=Bowers AJ, Scully S, Boylan JF |title=SKIP3, a novel Drosophila tribbles ortholog, is overexpressed in human tumors and is regulated by hypoxia. |journal=Oncogene |volume=22 |issue= 18 |pages= 2823-35 |year= 2003 |pmid= 12743605 |doi= 10.1038/sj.onc.1206367 }}
*{{cite journal   |vauthors=Kiss-Toth E, Bagstaff SM, Sung HY, etal |title=Human tribbles, a protein family controlling mitogen-activated protein kinase cascades. |journal=J. Biol. Chem. |volume=279 |issue= 41 |pages= 42703–8 |year= 2004 |pmid= 15299019 |doi= 10.1074/jbc.M407732200 }}
*{{cite journal | author=Du K, Herzig S, Kulkarni RN, Montminy M |title=TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver. |journal=Science |volume=300 |issue= 5625 |pages= 1574-7 |year= 2003 |pmid= 12791994 |doi= 10.1126/science.1079817 }}
*{{cite journal   |vauthors=Gerhard DS, Wagner L, Feingold EA, etal |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504  | pmc=528928 }}
*{{cite journal | author=Huang J, Teng L, Liu T, ''et al.'' |title=Identification of a novel serine/threonine kinase that inhibits TNF-induced NF-kappaB activation and p53-induced transcription. |journal=Biochem. Biophys. Res. Commun. |volume=309 |issue= 4 |pages= 774-8 |year= 2003 |pmid= 13679039 |doi= }}
*{{cite journal   |vauthors=Ohoka N, Yoshii S, Hattori T, etal |title=TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death. |journal=EMBO J. |volume=24 |issue= 6 |pages= 1243–55 |year= 2005 |pmid= 15775988 |doi= 10.1038/sj.emboj.7600596  | pmc=556400 }}
*{{cite journal | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal  |vauthors=Ord D, Ord T |title=Characterization of human NIPK (TRB3, SKIP3) gene activation in stressful conditions. |journal=Biochem. Biophys. Res. Commun. |volume=330 |issue= 1 |pages= 210–8 |year= 2005 |pmid= 15781252 |doi= 10.1016/j.bbrc.2005.02.149 }}
*{{cite journal | author=Kiss-Toth E, Bagstaff SM, Sung HY, ''et al.'' |title=Human tribbles, a protein family controlling mitogen-activated protein kinase cascades. |journal=J. Biol. Chem. |volume=279 |issue= 41 |pages= 42703-8 |year= 2004 |pmid= 15299019 |doi= 10.1074/jbc.M407732200 }}
*{{cite journal   |vauthors=Prudente S, Hribal ML, Flex E, etal |title=The functional Q84R polymorphism of mammalian Tribbles homolog TRB3 is associated with insulin resistance and related cardiovascular risk in Caucasians from Italy. |journal=Diabetes |volume=54 |issue= 9 |pages= 2807–11 |year= 2005 |pmid= 16123373 |doi=10.2337/diabetes.54.9.2807  }}
*{{cite journal  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal   |vauthors=Schwarzer R, Dames S, Tondera D, etal |title=TRB3 is a PI 3-kinase dependent indicator for nutrient starvation. |journal=Cell. Signal. |volume=18 |issue= 6 |pages= 899–909 |year= 2006 |pmid= 16129579 |doi= 10.1016/j.cellsig.2005.08.002 }}
*{{cite journal | author=Ohoka N, Yoshii S, Hattori T, ''et al.'' |title=TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death. |journal=EMBO J. |volume=24 |issue= 6 |pages= 1243-55 |year= 2005 |pmid= 15775988 |doi= 10.1038/sj.emboj.7600596 }}
*{{cite journal   |vauthors=Stelzl U, Worm U, Lalowski M, etal |title=A human protein-protein interaction network: a resource for annotating the proteome. |journal=Cell |volume=122 |issue= 6 |pages= 957–68 |year= 2005 |pmid= 16169070 |doi= 10.1016/j.cell.2005.08.029 }}
*{{cite journal | author=Ord D, Ord T |title=Characterization of human NIPK (TRB3, SKIP3) gene activation in stressful conditions. |journal=Biochem. Biophys. Res. Commun. |volume=330 |issue= 1 |pages= 210-8 |year= 2005 |pmid= 15781252 |doi= 10.1016/j.bbrc.2005.02.149 }}
*{{cite journal   |vauthors=Matsushima R, Harada N, Webster NJ, etal |title=Effect of TRB3 on insulin and nutrient-stimulated hepatic p70 S6 kinase activity. |journal=J. Biol. Chem. |volume=281 |issue= 40 |pages= 29719–29 |year= 2006 |pmid= 16887816 |doi= 10.1074/jbc.M511636200 }}
*{{cite journal | author=Prudente S, Hribal ML, Flex E, ''et al.'' |title=The functional Q84R polymorphism of mammalian Tribbles homolog TRB3 is associated with insulin resistance and related cardiovascular risk in Caucasians from Italy. |journal=Diabetes |volume=54 |issue= 9 |pages= 2807-11 |year= 2005 |pmid= 16123373 |doi= }}
*{{cite journal   |vauthors=Koh HJ, Arnolds DE, Fujii N, etal |title=Skeletal muscle-selective knockout of LKB1 increases insulin sensitivity, improves glucose homeostasis, and decreases TRB3. |journal=Mol. Cell. Biol. |volume=26 |issue= 22 |pages= 8217–27 |year= 2007 |pmid= 16966378 |doi= 10.1128/MCB.00979-06 | pmc=1636784 }}
*{{cite journal | author=Schwarzer R, Dames S, Tondera D, ''et al.'' |title=TRB3 is a PI 3-kinase dependent indicator for nutrient starvation. |journal=Cell. Signal. |volume=18 |issue= 6 |pages= 899-909 |year= 2006 |pmid= 16129579 |doi= 10.1016/j.cellsig.2005.08.002 }}
*{{cite journal | author=Stelzl U, Worm U, Lalowski M, ''et al.'' |title=A human protein-protein interaction network: a resource for annotating the proteome. |journal=Cell |volume=122 |issue= 6 |pages= 957-68 |year= 2005 |pmid= 16169070 |doi= 10.1016/j.cell.2005.08.029 }}
*{{cite journal | author=Matsushima R, Harada N, Webster NJ, ''et al.'' |title=Effect of TRB3 on insulin and nutrient-stimulated hepatic p70 S6 kinase activity. |journal=J. Biol. Chem. |volume=281 |issue= 40 |pages= 29719-29 |year= 2006 |pmid= 16887816 |doi= 10.1074/jbc.M511636200 }}
*{{cite journal  | author=Koh HJ, Arnolds DE, Fujii N, ''et al.'' |title=Skeletal muscle-selective knockout of LKB1 increases insulin sensitivity, improves glucose homeostasis, and decreases TRB3. |journal=Mol. Cell. Biol. |volume=26 |issue= 22 |pages= 8217-27 |year= 2007 |pmid= 16966378 |doi= 10.1128/MCB.00979-06 }}
}}
{{refend}}
{{refend}}


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Latest revision as of 07:15, 10 January 2019

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Tribbles homolog 3 is a protein that in humans is encoded by the TRIB3 gene.[1][2][3]

Function

The protein encoded by this gene is a putative protein kinase that is induced by the transcription factor NF-kappaB. It is a pseudoenzyme that is thought to be a negative regulator of NF-kappaB, and can also sensitize cells to TNF- and TRAIL-induced apoptosis. In addition, this protein has been reported to negatively regulate the cell survival serine-threonine kinase AKT1.[3] TRIB3 has recently been associated with neuronal signalling, and like TRIB1 and TRIB2, could be considered as a potential allosteric drug target [4][5]

Interactions

TRIB3 has been shown to interact with:

References

  1. 1.0 1.1 Du K, Herzig S, Kulkarni RN, Montminy M (Jun 2003). "TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver". Science. 300 (5625): 1574–7. doi:10.1126/science.1079817. PMID 12791994.
  2. Hegedus Z, Czibula A, Kiss-Toth E (Aug 2006). "Tribbles: novel regulators of cell function; evolutionary aspects". Cell Mol Life Sci. 63 (14): 1632–41. doi:10.1007/s00018-006-6007-9. PMID 16715410.
  3. 3.0 3.1 "Entrez Gene: TRIB3 tribbles homolog 3 (Drosophila)".
  4. Eyers PA, Keeshan K, Kannan N (2016). "Tribbles in the 21st Century: The Evolving Roles of Tribbles Pseudokinases in Biology and Disease". Trends in Cell Biology. In Press (9): S0962-8924(16)30178-7. doi:10.1016/j.tcb.2016.11.002. PMC 5382568. PMID 27908682.
  5. Foulkes DM, Byrne DP, Eyers PA (2015). "Tribbles pseudokinases: novel targets for chemical biology and drug discovery?". Biochemical Society Transactions. 43 (5): 1095–1103. doi:10.1042/BST20150109. PMID 26517930.
  6. 6.0 6.1 6.2 6.3 Zhou Y, Li L, Liu Q, Xing G, Kuai X, Sun J, Yin X, Wang J, Zhang L, He F (May 2008). "E3 ubiquitin ligase SIAH1 mediates ubiquitination and degradation of TRB3". Cell. Signal. 20 (5): 942–8. doi:10.1016/j.cellsig.2008.01.010. PMID 18276110.
  7. Bowers AJ, Scully S, Boylan JF (May 2003). "SKIP3, a novel Drosophila tribbles ortholog, is overexpressed in human tumors and is regulated by hypoxia". Oncogene. 22 (18): 2823–35. doi:10.1038/sj.onc.1206367. PMID 12743605.
  8. Wu M, Xu LG, Zhai Z, Shu HB (July 2003). "SINK is a p65-interacting negative regulator of NF-kappaB-dependent transcription". J. Biol. Chem. 278 (29): 27072–9. doi:10.1074/jbc.M209814200. PMID 12736262.

Further reading