FBXO31 is the chromosome 16q24.3 senescence gene, a candidate breast tumor suppressor, and a component of an SCF complex.
A BAC located in the 16q24.3 breast cancer loss of heterozygosity region was previously shown to restore cellular senescence when transferred into breast tumor cell lines. We have shown that FBXO31, although located just distal to this BAC, can induce cellular senescence in the breast cancer cell line MCF-7 and is the likely candidate senescence gene. FBXO31 has properties consistent with a tumor suppressor, because ectopic expression of FBXO31 in two breast cancer cell lines inhibited colony growth on plastic and inhibited cell proliferation in the MCF-7 cell line. In addition, compared with the relative expression in normal breast, levels of FBXO31 were down-regulated in breast tumor cell lines and primary tumors. FBXO31 was cell cycle regulated in the breast cell lines MCF-10A and SKBR3 with maximal expression from late G(2) to early G(1) phase. Ectopic expression of FBXO31 in the breast cancer cell line MDA-MB-468 resulted in the accumulation of cells at the G(1) phase of the cell cycle. FBXO31 contains an F-box domain and is associated with the proteins Skp1, Roc-1, and Cullin-1, suggesting that FBXO31 is a component of a SCF ubiquitination complex. We propose that FBXO31 functions as a tumor suppressor by generating SCF(FBXO31) complexes that target particular substrates, critical for the normal execution of the cell cycle, for ubiquitination and subsequent degradation.
Kumar
Raman
R
Breast Cancer Genetics Group, Dame Roma Mitchell Cancer Research Laboratories, Department of Medicine, University of Adelaide and Hanson Institute, Institute of Medical and Veterinary Science Adelaide, Australia.
Neilsen
Paul M
PM
Crawford
Joanne
J
McKirdy
Ross
R
Lee
Jaclyn
J
Powell
Jason A
JA
Saif
Zarqa
Z
Martin
Julie M
JM
Lombaerts
Marc
M
Cornelisse
Cees J
CJ
Cleton-Jansen
Anne-Marie
AM
Callen
David F
DF
D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000235:genetics*; D022202:Chromosomes, Artificial, Bacterial; D002885:Chromosomes, Human, Pair 16; D003114:Colony-Forming Units Assay; D044842:Cullin Proteins / Q000378:metabolism; D044783:F-Box Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D016193:G1 Phase; D016195:G2 Phase; D016147:Genes, Tumor Suppressor; D006801:Humans; D047468:Immunoprecipitation; D007668:Kidney / Q000378:metabolism; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C100318:Cullin 1; D044842:Cullin Proteins; D044783:F-Box Proteins; C507917:FBXO31 protein, human; C479529:RBX1 protein, human; D025521:Tumor Suppressor Proteins