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Query: Extended Site:
Characterization of the KCTD protein family: key factors in several biological processes
Contact person: Laura Zaccaro, lzaccarounina.it


Description ▼
The family of human proteins containing a potassium channel tetramerization domain (KCTD) includes 21 members that are implicated in very important biological processes. KCTD11/REN, the best-characterized member of the family to date, is a negative regulator of the Hedgehog pathway and plays an important role in the tumorigenesis of medulloblastoma, a severe and widespread solid cancer of the childhood. Very recently it has been shown that it is involved in the ubiquitination of HDAC1 by acting, in complex with Cullin3, as an E3 ubiquitin ligase (1). The molecular and structural characterization of KCTD11 has shown that this tetrameric protein is involved in giant macromolecular complexes with its biological partners (Cul3, Rbx1, E2) (2). The development of molecules that are able to interfere with the function of this protein will likely have a relevant impact in the definition of the molecular basis of tumorigenesis. In this scenario, we have recently developed peptides, derived from the Cl3 protein, that are able to bind KCTD11 and other members of this protein family (3). Current activities are focused on the optimization of these molecules and on the characterization of structure-function relations for other members of the KCTD family

Actors ▼
Laura Zaccaro, lzaccarounina.it
Giuseppina De Simone, gdesimonunina.it
Simona Maria Monti, marmontiunina.it
Vincenzo Alterio, vincenzo.alterio@ibb.cnr.it
EmiliaMaria Pedone, empedoneunina.it
Luigi Vitagliano, luigi.vitaglianocnr.it
Sonia Di Gaetano, digaetanunina.it

Keywords ▼
Tumorigenesis, Medulloblastoma, KCTD, Molecular Design,

Research Areas ▼
Malattie Neoplastiche, 

Figures ▼

Figure 1. 3D model of the complex between the POZ/BTB domain of KCTD11 (cyan) with Cul3 (red), Rbx1 (yellow), and E2 (green)

Figure 2. 3D model of the complex between KCTD5 (red) with Cul3 (blue)


Selected Papers ▼
1) Canettieri G, Di Marcotullio L, Greco A, Coni S, Antonucci L, Infante P, Pietrosanti L, De Smaele E, Ferretti E, Miele E, Pelloni M, De Simone G, Pedone EM, Gallinari P, Giorgi A, Steinkhler C, Vitagliano L, Pedone C, Schinin ME, Screpanti I, Gulino A Histone deacetylase and Cullin3-REN (KCTD11) ubiquitin ligase interplay regulates Hedgehog signalling through Gli acetylation. Nature Cell Biology 2010, 12: 132-42. 2) Correale S, Pirone L, Di Marcotullio L, De Smaele E, Greco A, Mazz D, Moretti M, Alterio V, Vitagliano L, Di Gaetano S, Gulino A, Pedone EM. Molecular organization of the cullin E3 ligase adaptor KCTD11. Biochimie 2011, 17: 373-6. 3) Pirone L, Correale S, Paola I, Zaccaro L, De Simone G, Vitagliano L, Pedone EM, Di Gaetano S. Design, synthesis and characterization of a peptide able to bind proteins of the KCTD family: implications for KCTD-cullin 3 recognition. Journal of Peptide Science 2011, 93: 715-24

Related Activities ▼
No results.

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* The RNA-binding protein ESRP1 promotes human colorectal cancer progression (36 views)
Fagoonee S, Picco G, Orso F, Arrigoni A, Longo DL, Forni M, Scarfo I, Cassenti A, Piva R, Cassoni P, Silengo L, Tolosano E, Aime S, Taverna D, Pandolfi PP, Brancaccio M, Medico E, Altruda F
Oncotarget (ISSN: 1949-2553electronic, 1949-2553linking), 2017 Feb 07; 8(6): 10007-10024.

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* Dual role of GRK5 in cancer development and progression (46 views)
Gambardella J, Franco A, Giudice CD, Fiordelisi A, Cipolletta E, Ciccarelli M, Trimarco B, Iaccarino G, Sorriento D
Transl Med Unisa (ISSN: 2239-9747electronic, 2239-9747linking), 2016 May 16; 14: 28-37.

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* HER2-mediated anticancer drug delivery: strategies to prepare targeting ligands highly specific for the receptor (152 views)
Calce E, Monfregola L, Saviano M, De Luca S
Curr Med Chem (ISSN: 1875-533xelectronic, 0929-8673linking), 2015 May 20; 22(21): 2525-2538.

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* SIRT1 gene expression upon genotoxic damage is regulated by APE1 through nCaRE-promoter elements (89 views)
Antoniali G, Lirussi L, D'Ambrosio C, Dal Piaz F, Vascotto C, Casarano E, Marasco D, Scaloni A, Fogolari F, Tell G
Molecular Biology Of The Cell (ISSN: 1059-1524), 2014 Feb 15; 25(4): 532-547.

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* Quercetin: a pleiotropic kinase inhibitor against cancer (92 views)
Russo GL, Russo M, Spagnuolo C, Tedesco I, Bilotto S, Iannitti R, Palumbo R
Cancer Treat Res (ISSN: 0927-3042), 2014; 159: 185-205.

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* Neuroblastoma tumorigenesis is regulated through the Nm23-H1/h-Prune C-terminal interaction (127 views)
Carotenuto M, Pedone E, Diana D, de Antonellis P, Džeroski S, Marino N, Navas L, Di Dato V, Scoppettuolo MN, Cimmino F, Correale S, Pirone L, Monti SM, Bruder E, Zenko B, Slavkov I, Pastorino F, Ponzoni M, Schulte JH, Schramm A, Eggert A, Westermann F, Arrigoni G, Accordi B, Basso G, Saviano M, Fattorusso R, Zollo M
Sci Rep (ISSN: 2045-2322, 2045-2322electronic), 2013 Mar 1; 3: 1351-1351.

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* Carbonic anhydrase IX: Biochemical and crystallographic characterization of a novel antitumor target (82 views)
De Simone G, Supuran CT
Biochim Biophys Acta (ISSN: 1570-9639, 0006-3002, 0925-4439), 2010 Feb; 1804(2): 404-409.

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* Drug design studies of the novel antitumor targets carbonic anhydrase IX and XII (120 views)
Guler OO, De Simone G, Supuran CT
Curr Med Chem (ISSN: 0929-8673, 1875-533x, 1875-533xelectronic), 2010; 17(15): 1516-1526.

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* Crystal structure of the catalytic domain of the tumor-associated human carbonic anhydrase IX (99 views)
Alterio V, Hilvo M, Di Fiore A, Supuran CT, Pan P, Parkkila S, Scaloni A, Pastorek J, Pastorekova S, Pedone C, Scozzafava A, Monti SM, De Simone G
Proc Natl Acad Sci U S A (ISSN: 0027-8424, 1091-6490, 0027-8424print), 2009 Sep 22; 106(38): 16233-16238.

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9 Records (8 excluding Abstracts and Conferences).
Total impact factor: 49.991 (44.913 excluding Abstracts and Conferences).
Total 5-year impact factor: 50.637 (45.559 excluding Abstracts and Conferences).



Your bibliography query: ([btitle, keywords, abstract] TUMORIGENESIS)



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