Cerebral Cavernous Malformation


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2007 JUL 17 -- A new study, "PDCD10 interacts with Ste20-related kinase MST4 to promote cell growth and transformation via modulation of the ERK pathway," is now available. According to recent research from Beijing, People's Republic of China, "PDCD10 (programmed cell death 10, TFAR15), a novel protein associated with cell apoptosis has been recently implicated in mutations associated with Cerebral Cavernous Malformations (CCM). Yeast two-hybrid screening revealed that PDCD10 interacts with MST4, a member of Ste20-related kinases."

"This interaction was confirmed by coimmunoprecipitation and colocalization assays in mammalian cells. Furthermore, the co-overexpression of PDCD10 and MST4 promoted cell proliferation and transformation via modulation of the extracellular signal-regulated kinase (ERK) pathway. Potent short interfering RNAs (siRNAs) against PDCD10 (siPDCD10) and MST4 (siMST4) were designed to specifically inhibit the expression of PDCD10 and MST4 mRNA, respectively. The induction of siPDCD10 or siMST4 resulted in decreased expression of endogenous PDCD10 or MST4, which was accompanied by reduced ERK activity and attenuated cell growth and anchorage-independent growth. On the other hand, siMST4 had similar effects in PDCD10-overexpressed cells. And more importantly, we confirmed that either overexpressing or endogenous PDCD10 can increase the MST4 kinase activity in vitro," wrote X. Ma and colleagues, Peking University.

The researchers concluded: "Our results demonstrated that PDCD10 modulation of ERK signaling was mediated by MST4, and PDCD10 could be a regulatory adaptor necessary for MST4 function, suggesting a link between cerebral cavernous malformation pathogenesis and the ERK-MAPK cascade via PDCD10/MST4."

Ma and colleagues published their study in Molecular Biology of the Cell (PDCD10 interacts with Ste20-related kinase MST4 to promote cell growth and transformation via modulation of the ERK pathway. Molecular Biology of the Cell, 2007;18(6):1965-78).

For additional information, contact X. Ma, School of Basic Medicine and Human Disease Genomics Center, Dept. of Immunology, Peking University, Beijing 100083, China.

Publisher contact information for the journal Molecular Biology of the Cell is: American Society Cell Biology, 8120 Woodmont Avenue, Ste. 750, Bethesda, MD 20814-2755, USA.

Keywords: People's Republic of China, Beijing, Cell Biology, Molecular Biology.

This article was prepared by Life Science Weekly editors from staff and other reports. Copyright 2007, Life Science Weekly via NewsRx.com.