RGD Reference Report - Inhibition of cellular proliferation by the Wilms tumor suppressor WT1 requires association with the inducible chaperone Hsp70.

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Inhibition of cellular proliferation by the Wilms tumor suppressor WT1 requires association with the inducible chaperone Hsp70.
Authors:	Maheswaran, S Englert, C Zheng, G Lee, SB Wong, J Harkin, DP Bean, J Ezzell, R Garvin, AJ McCluskey, RT DeCaprio, JA Haber, DA
Citation:	Maheswaran S, etal., Genes Dev. 1998 Apr 15;12(8):1108-20.
RGD ID:	8554177
Pubmed:	PMID:9553041 (View Abstract at PubMed)
PMCID:	PMC316709 (View Article at PubMed Central)
The Wilms tumor suppressor WT1 encodes a zinc finger transcription factor that is expressed in glomerular podocytes during a narrow window in kidney development. By immunoprecipitation and protein microsequencing analysis, we have identified a major cellular protein associated with endogenous WT1 to be the inducible chaperone Hsp70. WT1 and Hsp70 are physically associated in embryonic rat kidney cells, in primary Wilms tumor specimens and in cultured cells with inducible expression of WT1. Colocalization of WT1 and Hsp70 is evident within podocytes of the developing kidney, and Hsp70 is recruited to the characteristic subnuclear clusters that contain WT1. The amino-terminal transactivation domain of WT1 is required for binding to Hsp70, and expression of that domain itself is sufficient to induce expression of Hsp70 through the heat shock element (HSE). Substitution of a heterologous Hsp70-binding domain derived from human DNAJ is sufficient to restore the functional properties of a WT1 protein with an amino-terminal deletion, an effect that is abrogated by a point mutation in DNAJ that reduces binding to Hsp70. These observations indicate that Hsp70 is an important cofactor for the function of WT1, and suggest a potential role for this chaperone during kidney differentiation.

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Molecular Function

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Hspa1a	Rat	protein binding	enables	IPI	UniProtKB:P49952	PMID:9553041	UniProt
Hspa1b	Rat	protein binding	enables	IPI	UniProtKB:P49952	PMID:9553041	UniProt
Wt1	Rat	protein binding	enables	IPI	UniProtKB:P0DMW0	PMID:9553041	UniProt
Wt1	Rat	protein binding	enables	IPI	UniProtKB:P0DMW1	PMID:9553041	UniProt

Objects Annotated

Genes (Rattus norvegicus)

Hspa1a (heat shock protein family A (Hsp70) member 1A)

Hspa1b (heat shock protein family A (Hsp70) member 1B)

Wt1 (WT1 transcription factor)

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Inhibition of cellular proliferation by the Wilms tumor suppressor WT1 requires association with the inducible chaperone Hsp70.