US scientists have revealed a new role for a protein called RNF5 in acute myeloid leukaemia (AML). High expression of the protein in patients with AML is linked to a poor prognosis, as it aids growth of AML cells, the researchers say.
Dr Ze’ev Ronai, from Sanford Burnham Prebys Medical Discovery Institute in California, and colleagues have been studying the role of RNF5 in various cancers. The normal role of RNF5 is to mark other proteins for destruction. However, in their recent studies they were surprised to find that it works with another protein called RBBP4 to control the activity of genes implicated in AML.
Their findings were published in Nature Communications. First author Dr Ali Khateb added: “When you don't have RNF5 in the cells, there is less recruitment of RBBP4 to the target genes, leading to their increased expression – and this inhibits AML growth.”
In lab tests, they found that inhibition of RNF5 decreases AML cell growth, and delays leukaemogenesis in mice, prolonging their survival. The team found that blocking the production of RNF4 or RBBP4 increases the sensitivity of AML cells to drugs called HDAC inhibitors.
Dr Ronai said: “AML cells are highly dependent on the RNF5 protein. If we inhibit it, AML cells don't survive. We can also use RNF5 levels to stratify patients for specific treatments. For example, if AML patients have low levels of RNF5 or RBBP4, they respond better to HDAC inhibitors, which are targeted treatments already used in the clinic.”
Khateb A, Deshpande A, Feng Y, Finlay D, Lee JS, Lazar I, Fabre B, Li Y, Fujita Y, Zhang T, Yin J, Pass I, Livneh I, Jeremias I, Burian C, Mason JR, Almog R, Horesh N, Ofran Y, Brown K, Vuori K, Jackson M, Ruppin E, Deshpande AJ, Ronai ZA. (2021) “RNF5 Regulation of RBBP4 Determines Acute Myeloid Leukemia Growth and Susceptibility to Histone Deacetylase Inhibitors.” Nature Communications, doi: 10.1038/s41467-021-25664-7
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