8caf

Structural highlights

Function

CUL1_HUMAN Core component of multiple cullin-RING-based SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as a rigid scaffold that organizes the SKP1-F-box protein and RBX1 subunits. May contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of CTNNB1 and participate in Wnt signaling. SCF(FBXW11) directs ubiquitination of phosphorylated NFKBIA. SCF(BTRC) directs ubiquitination of NFKBIB, NFKBIE, ATF4, SMAD3, SMAD4, CDC25A, FBXO5 and probably NFKB2. SCF(SKP2) directs ubiquitination of phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. SCF(SKP2) directs ubiquitination of ORC1, CDT1, RBL2, ELF4, CDKN1A, RAG2, FOXO1A, and probably MYC and TAL1. SCF(FBXW7) directs ubiquitination of cyclin E, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1. SCF(FBXW2) directs ubiquitination of GCM1. SCF(FBXO32) directs ubiquitination of MYOD1. SCF(FBXO7) directs ubiquitination of BIRC2 and DLGAP5. SCF(FBXO33) directs ubiquitination of YBX1. SCF(FBXO11) does not seem to direct ubiquitination of TP53. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(Cyclin F) directs ubiquitination of CP110 (By similarity).^{[1] [2] [3] [4] [5]}

References

1. ↑ Michel JJ, Xiong Y. Human CUL-1, but not other cullin family members, selectively interacts with SKP1 to form a complex with SKP2 and cyclin A. Cell Growth Differ. 1998 Jun;9(6):435-49. PMID:9663463
2. ↑ Tintignac LA, Lagirand J, Batonnet S, Sirri V, Leibovitch MP, Leibovitch SA. Degradation of MyoD mediated by the SCF (MAFbx) ubiquitin ligase. J Biol Chem. 2005 Jan 28;280(4):2847-56. Epub 2004 Nov 5. PMID:15531760 doi:M411346200
3. ↑ Yang CS, Yu C, Chuang HC, Chang CW, Chang GD, Yao TP, Chen H. FBW2 targets GCMa to the ubiquitin-proteasome degradation system. J Biol Chem. 2005 Mar 18;280(11):10083-90. Epub 2005 Jan 8. PMID:15640526 doi:M413986200
4. ↑ Lovly CM, Yan L, Ryan CE, Takada S, Piwnica-Worms H. Regulation of Chk2 ubiquitination and signaling through autophosphorylation of serine 379. Mol Cell Biol. 2008 Oct;28(19):5874-85. doi: 10.1128/MCB.00821-08. Epub 2008 Jul , 21. PMID:18644861 doi:10.1128/MCB.00821-08
5. ↑ Isobe T, Hattori T, Kitagawa K, Uchida C, Kotake Y, Kosugi I, Oda T, Kitagawa M. Adenovirus E1A inhibits SCF(Fbw7) ubiquitin ligase. J Biol Chem. 2009 Oct 9;284(41):27766-79. Epub 2009 Aug 13. PMID:19679664 doi:M109.006809