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Link between p34(cdc2) and Punctate Palmoplantar Keratoderma.
p34(cdc2) is a kinase which is an essential nuclear protein for mitosis in human cells. During the prophase/metaphase transition the inactive phosphorylated form of p34(cdc2) is dephosphorylated to yield the active form of the protein. Recent data published in Nature Genetics (14 October 2012) from Pohler et al link a heterozygous loss-of-function mutation to clinical manifestations of punctate palmoplantar keratoderma. Knockdown of the alpha- and gamma-adaptin-binding protein p34 gene (AAGAB) in keratinocytes led to an increase in cell division and elevated levels of EGFR expression and tyrosine kinase phosphorylation. It therefore seems likely that p34 plays a key role in the hyper-proliferation of cells in this disorder.