Researchers from University of Dundee have identified an important function of one cancer suppressor gene, which may help scientists better understand how this gene confront the influences of oncogene mutation. This study was published in PNAS.

Dual-specificity phosphatase 5 (DUSP5) is one of four mammalian inducible, nuclear mitogen-activated protein kinase (MAPK) phosphatases (MKPs). However, DUSP5 is unique within this group in targeting only the classical extracellular signal-regulated kinases 1 and 2(ERK). Ras/ERK signaling is frequently deregulated in human cancers due to activating mutations in pathway.

Ras/extracelluar signal-regulated kinase (ERK) signaling is implicated in human cancer development and progression. ERK activation also results in the expression of MAP kinase phosphatases(MKPs) that inactivate ERK. However, it is currently unclear how MKPs regulate the oncogenic potential of the Ras/ERK pathway.

In this study, scientists identify the MKP encoded by dual-specificity phosphatase 5 (DUSP5) as both a key regulator of nuclear ERK activity and a tumor suppressor in the DMBA/TPA model of Harvey Ras (Hras)-induced skin carcinogenesis. DUSP5 loss results in increased HRas/ERK-inducible SerpinB2 expression, which causes increased skin cancer sensitivity.

Their results establish a key role for DUSP5 in the regulation of oncogenic ERK signaling and suggest that this enzyme may play a wider role in tumors containing activated Ras.

Reference:

Rushworth L K, Kidger A M, Delavaine L, et al. Dual-specificity phosphatase 5 regulates nuclear ERK activity and suppresses skin cancer by inhibiting mutant Harvey-Ras (HRasQ61L)-driven SerpinB2 expression[J]. Proceedings of the National Academy of Sciences, 2014, 111(51): 18267-18272.