F-box/WD repeat-containing protein 7

Definition:

Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Recognizes and binds phosphorylated sites/phosphodegrons within target proteins and thereafter brings them to the SCF complex for ubiquitination. Identified substrates include cyclin-E (CCNE1 or CCNE2), DISC1, JUN, MYC, NOTCH1 released notch intracellular domain (NICD), NFE2L1, NOTCH2, MCL1, RICTOR, and probably PSEN1. Acts as a negative regulator of JNK signaling by binding to phosphorylated JUN and promoting its ubiquitination and subsequent degradation. Involved in bone homeostasis and negative regulation of osteoclast differentiation. Regulates the amplitude of the cyclic expression of hepatic core clock genes and genes involved in lipid and glucose metabolism via ubiquitination and proteasomal degradation of their transcriptional repressor NR1D1; CDK1-dependent phosphorylation of NR1D1 is necessary for SCF(FBXW7)-mediated ubiquitination. Also able to promote 'Lys-63'-linked ubiquitination in response to DNA damage. The SCF(FBXW7) complex facilitates double-strand break repair following phosphorylation by ATM: phosphorylation promotes localization to sites of double-strand breaks and 'Lys-63'-linked ubiquitination of phosphorylated XRCC4, enhancing DNA non-homologous end joining.

References:

[1]. K Yalla, et al. FBXW7 regulates DISC1 stability via the ubiquitin-proteosome system. Mol Psychiatry. 2018 May;23(5):1278-1286. [Content Brief]

[2]. Nikita Popov, et al. The ubiquitin-specific protease USP28 is required for MYC stability. Nat Cell Biol. 2007 Jul;9(7):765-74. [Content Brief]

[3]. Xuan Zhao, et al. Circadian Amplitude Regulation via FBXW7-Targeted REV-ERBα Degradation. Cell. 2016 Jun 16;165(7):1644-1657. [Content Brief]

[4]. Nikita Popov, et al. Fbw7 and Usp28 regulate myc protein stability in response to DNA damage. Cell Cycle. 2007 Oct 1;6(19):2327-31. [Content Brief]

[5]. Abdolrahman S Nateri, et al. The ubiquitin ligase SCFFbw7 antagonizes apoptotic JNK signaling. Science. 2004 Feb 27;303(5662):1374-8. [Content Brief]

[6]. Qiang Zhang, et al. FBXW7 Facilitates Nonhomologous End-Joining via K63-Linked Polyubiquitylation of XRCC4. Mol Cell. 2016 Feb 4;61(3):419-433. [Content Brief]

[7]. Masayoshi Yada, et al. Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7. EMBO J. 2004 May 19;23(10):2116-25. [Content Brief]

[8]. Veronika Reiterer, et al. The pseudophosphatase STYX targets the F-box of FBXW7 and inhibits SCFFBXW7 function. EMBO J. 2017 Feb 1;36(3):260-273. [Content Brief]

[9]. G Wu, et al. SEL-10 is an inhibitor of notch signaling that targets notch for ubiquitin-mediated protein degradation. Mol Cell Biol. 2001 Nov;21(21):7403-15. [Content Brief]

[10]. Hidefumi Fukushima, et al. NOTCH2 Hajdu-Cheney Mutations Escape SCFFBW7-Dependent Proteolysis to Promote Osteoporosis. Mol Cell. 2017 Nov 16;68(4):645-658.e5. [Content Brief]

[11]. Jinhe Li, et al. SEL-10 interacts with presenilin 1, facilitates its ubiquitination, and alters A-beta peptide production. J Neurochem. 2002 Sep;82(6):1540-8. [Content Brief]

[12]. Xiao-Xin Sun, et al. The nucleolar ubiquitin-specific protease USP36 deubiquitinates and stabilizes c-Myc. Proc Natl Acad Sci U S A. 2015 Mar 24;112(12):3734-9. [Content Brief]

[13]. H Strohmaier, et al. Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line. Nature. 2001 Sep 20;413(6853):316-22. [Content Brief]

[14]. Sang-Hyun Min, et al. Negative regulation of the stability and tumor suppressor function of Fbw7 by the Pin1 prolyl isomerase. Mol Cell. 2012 Jun 29;46(6):771-83. [Content Brief]

[15]. Bing Hao, et al. Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated substrate recognition by SCF ubiquitin ligases. Mol Cell. 2007 Apr 13;26(1):131-43. [Content Brief]

[16]. David M Duda, et al. Structure of a glomulin-RBX1-CUL1 complex: inhibition of a RING E3 ligase through masking of its E2-binding surface. Mol Cell. 2012 Aug 10;47(3):371-82. [Content Brief]

[17]. Junghui Koo, et al. Rictor Undergoes Glycogen Synthase Kinase 3 (GSK3)-dependent, FBXW7-mediated Ubiquitination and Proteasomal Degradation. J Biol Chem. 2015 May 29;290(22):14120-9. [Content Brief]

[18]. Maryna Gorelik, et al. Inhibition of SCF ubiquitin ligases by engineered ubiquitin variants that target the Cul1 binding site on the Skp1-F-box interface. Proc Natl Acad Sci U S A. 2016 Mar 29;113(13):3527-32. [Content Brief]

Biomedical Dictionary

The Biomedical Dictionary is a comprehensive and professional collection of biological academic terms and subject datas. All explanations are supported by authoritative books or high impact factor literatures, and you can acquire accurate explanations of the biomedical terms you want to know.

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z #

Name
Email *

	Sorry, but the email address you supplied was invalid.