F-box/WD repeat-containing protein 8

Definition:

Substrate-recognition component of a Cul7-RING ubiquitin-protein ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. The Cul7-RING(FBXW8) complex mediates ubiquitination and consequent degradation of GORASP1, acting as a component of the ubiquitin ligase pathway that regulates Golgi morphogenesis and dendrite patterning in brain. Mediates ubiquitination and degradation of IRS1 in a mTOR-dependent manner: the Cul7-RING(FBXW8) complex recognizes and binds IRS1 previously phosphorylated by S6 kinase (RPS6KB1 or RPS6KB2). The Cul7-RING(FBXW8) complex also mediates ubiquitination of MAP4K1/HPK1: recognizes and binds autophosphorylated MAP4K1/HPK1, leading to its degradation, thereby affecting cell proliferation and differentiation. Associated component of the 3M complex, suggesting that it mediates some of 3M complex functions.

References:

[1]. Jun Yan, et al. The 3M complex maintains microtubule and genome integrity. Mol Cell. 2014 Jun 5;54(5):791-804. [Content Brief]

[2]. Xinsong Xu, et al. The CUL7 E3 ubiquitin ligase targets insulin receptor substrate 1 for ubiquitin-dependent degradation. Mol Cell. 2008 May 23;30(4):403-14. [Content Brief]

[3]. Nadia Litterman, et al. An OBSL1-Cul7Fbxw8 ubiquitin ligase signaling mechanism regulates Golgi morphology and dendrite patterning. PLoS Biol. 2011 May;9(5):e1001060. [Content Brief]

[4]. Hua Wang, et al. The CUL7/F-box and WD repeat domain containing 8 (CUL7/Fbxw8) ubiquitin ligase promotes degradation of hematopoietic progenitor kinase 1. J Biol Chem. 2014 Feb 14;289(7):4009-17. [Content Brief]

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