Actin: a novel interaction partner of WT1 influencing its cell dynamic properties.
The Wilms' tumour suppressor, WT1, is a zinc finger protein with key roles in normal development of the genitourinary system and tumourigenesis. Mutations or deletion of WT1 result in a spectrum of developmental disorders and susceptibility to Wilms' tumour in children. Ectopic expression of Wt1 associated with oncogenic functions has been observed in a large number of malignancies, including haematological and solid cancers. Although Wt1 is predominantly a nuclear protein in normal tissues, it is mostly cytoplasmic in the majority of Wt1-expressing tumours. Actin was identified in this study as a new WT1 interaction partner both in the nucleus and in the cytoplasm. We confirmed this interaction both in vitro and in vivo and started to explore its functional significance. Perturbation of the actin cytoskeleton moved Wt1 off the polysome fraction in the cytoplasm, cancelled its nucleo-cytoplasmic shuttling and altered Wt1 DNA- and RNA-binding abilities. These data have implications for Wt1 functions in relation to RNA metabolism and response to cytoskeletal alterations in cancer cells. Thus, our findings could shed more light on the functions of both these proteins and possibly pave way for the development of new cancer therapies.
Dudnakova
T
T
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK.
Spraggon
L
L
Slight
J
J
Hastie
N
N
D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D051379:Mice; D011485:Protein Binding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D051381:Rats; D025721:WT1 Proteins / Q000378:metabolism*
D000199:Actins; D025721:WT1 Proteins