S-phase kinase-associated protein 2

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 involved in cell cycle progression, signal transduction and transcription. Specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition (By similarity). Degradation of CDKN1B/p27kip also requires CKS1. Recognizes target proteins ORC1, CDT1, RBL2, KMT2A/MLL1, CDK9, RAG2, FOXO1, UBP43, YTHDF2, and probably MYC, TOB1 and TAL1. Degradation of TAL1 also requires STUB1. Recognizes CDKN1A in association with CCNE1 or CCNE2 and CDK2. Promotes ubiquitination and destruction of CDH1 in a CK1-dependent manner, thereby regulating cell migration.; Through the ubiquitin-mediated proteasomal degradation of hepatitis C virus non-structural protein 5A, has an antiviral activity towards that virus.

References:

[1]. Hiroyuki Inuzuka, et al. Acetylation-dependent regulation of Skp2 function. Cell. 2012 Jul 6;150(1):179-93. [Content Brief]

[2]. Qili Fei, et al. YTHDF2 promotes mitotic entry and is regulated by cell cycle mediators. PLoS Biol. 2020 Apr 8;18(4):e3000664. [Content Brief]

[3]. Matjaz Barboric, et al. Ubiquitylation of Cdk9 by Skp2 facilitates optimal Tat transactivation. J Virol. 2005 Sep;79(17):11135-41. [Content Brief]

[4]. Yoshihiro Hiramatsu, et al. Degradation of Tob1 mediated by SCFSkp2-dependent ubiquitination. Cancer Res. 2006 Sep 1;66(17):8477-83. [Content Brief]

[5]. Hao Jiang, et al. Ubiquitylation of RAG-2 by Skp2-SCF links destruction of the V(D)J recombinase to the cell cycle. Mol Cell. 2005 Jun 10;18(6):699-709. [Content Brief]

[6]. Sara Tokarz, et al. The ISG15 isopeptidase UBP43 is regulated by proteolysis via the SCFSkp2 ubiquitin ligase. J Biol Chem. 2004 Nov 5;279(45):46424-30. [Content Brief]

[7]. Haojie Huang, et al. Skp2 inhibits FOXO1 in tumor suppression through ubiquitin-mediated degradation. Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1649-54. [Content Brief]

[8]. Binbin Xue, et al. ISG12a Restricts Hepatitis C Virus Infection through the Ubiquitination-Dependent Degradation Pathway. J Virol. 2016 Jul 11;90(15):6832-45. [Content Brief]

[9]. Lei Nie, et al. Ubiquitination and degradation of Tal1/SCL are induced by notch signaling and depend on Skp2 and CHIP. J Biol Chem. 2008 Jan 11;283(2):684-92. [Content Brief]

[10]. Wei Wang, et al. Ubiquitination of p21Cip1/WAF1 by SCFSkp2: substrate requirement and ubiquitination site selection. Biochemistry. 2005 Nov 8;44(44):14553-64. [Content Brief]

[11]. Yan Liu, et al. The ETS protein MEF is regulated by phosphorylation-dependent proteolysis via the protein-ubiquitin ligase SCFSkp2. Mol Cell Biol. 2006 Apr;26(8):3114-23. [Content Brief]

[12]. Juan Méndez, et al. Human origin recognition complex large subunit is degraded by ubiquitin-mediated proteolysis after initiation of DNA replication. Mol Cell. 2002 Mar;9(3):481-91. [Content Brief]

[13]. Donato Tedesco, et al. The pRb-related protein p130 is regulated by phosphorylation-dependent proteolysis via the protein-ubiquitin ligase SCF(Skp2). Genes Dev. 2002 Nov 15;16(22):2946-57. [Content Brief]

[14]. Natalie von der Lehr, et al. The F-box protein Skp2 participates in c-Myc proteosomal degradation and acts as a cofactor for c-Myc-regulated transcription. Mol Cell. 2003 May;11(5):1189-200. [Content Brief]

[15]. Xianghong Li, et al. The SCF(Skp2) ubiquitin ligase complex interacts with the human replication licensing factor Cdt1 and regulates Cdt1 degradation. J Biol Chem. 2003 Aug 15;278(33):30854-8. [Content Brief]

[16]. Han Liu, et al. Bimodal degradation of MLL by SCFSkp2 and APCCdc20 assures cell cycle execution: a critical regulatory circuit lost in leukemogenic MLL fusions. Genes Dev. 2007 Oct 1;21(19):2385-98. [Content Brief]

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