F-box proteiinien assosioituminen syöpään

Nat Rev Cancer. 2014 Apr;14(4):233-47. doi: 10.1038/nrc3700.

Roles of F-box proteins in cancer.

Wang Z¹, Liu P², Inuzuka H³, Wei W³.

Abstract

F-box proteins, which are the substrate-recognition subunits of SKP1-cullin 1-F-box protein (SCF) E3 ligase complexes, have pivotal roles in multiple cellular processes through ubiquitylation and subsequent degradation of target proteins. Dysregulation of F-box protein-mediated proteolysis leads to human malignancies. Notably, inhibitors that target F-box proteins have shown promising therapeutic potential, urging us to review the current understanding of how F-box proteins contribute to tumorigenesis. As the physiological functions for many of the 69 putative F-box proteins remain elusive, additional genetic and mechanistic studies will help to define the role of each F-box protein in tumorigenesis, thereby paving the road for the rational design of F-box protein-targeted anticancer therapies.

PMID:

24658274

PMCID:

PMC4306233

DOI:

10.1038/nrc3700

[Indexed for MEDLINE]

Free PMC Article

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Figure 1

Illustration of functional domains in the highlighted F-Box proteins, grouped by their potential functions in cancer that have been shown by available mouse models

On the basis of data from mouse genetics, pathological profiles and biochemical substrates identified for each F-box protein we group F-box proteins into four categories to indicate their roles in tumorigenesis: tumour suppressor (part a), oncogene (part b), context-dependent (part c) and undetermined (part d).

 β-TRCP, β-transducin repeat-containing protein; 

BH, β-helix;

 F, F-box motif;

 FBXL, F-box and leucine-rich repeat protein; 

FBXO, F-box only; 

FBXW, F-box/WD repeat-containing protein; 

HT, hemerythrin domain;

 IBR, in between ring fingers domain;

 L, leucine-rich repeat;

 Nop14, NOP14-like family domain;

 NosD, periplasmic copper-binding protein; 

PI31-prot-N, PI31 proteasome regulator amino-terminal domain; 

SKP2, S-phase kinase-associated protein 2; 

SPRY, SPLA and the ryanodine receptor domain; 

T, transmembrane region; Tr, D domain of β-TRCP; 

TRP, tetratricopeptide repeat; 

UH, UvrD/REP helicase N-terminal domain; 

UvrD, UvrD-like helicase C-terminal domain;

 W, WD40 repeat;

 Zu, putative zinc finger in N-recognin.