Characterization of the Expression and Function of a Novel BTB-kelch Protein DIP-2
Date Issued
2009
Date
2009
Author(s)
Lai, Chun-Kai
Abstract
DIP-2 is a member of the BTB-kelch protein family, of which several members are highly expressed in the nervous system and have been demonstrated to elicit neuronal functions, including neural morphogenesis and synapse transmission. However, little is known about the expression patterns of DIP-2 and its biological functions, although previous studies in our laboratory revealed that DIP-2 functions as a substrate adaptor of Cul3-based ubiquitin ligase to promote the ubiquitination of DAPK and PML. Here, we characterized the expression pattern of DIP-2 protein in the adult mouse brain and found its high expression levels in the cerebral cortex, the hippocampus, the olfactory bulb and the cerebellar cortex. Notably, DIP-2 displays both somatic and dendritic patterns in most regions observed, whereas it exhibits an axonal pattern in CA3 of hippocampus. In an attempt to study the function of DIP-2, we investigated the mechanism through which DIP-2 mediates PML protein degradation. First, we identified a role of CDK in DIP-2-mediated PML degradation. Furthermore, we demonstrated PML as the substrate of CDK1/2/4/6 in vitro and the Ser 518 residue as the major phosphorylation site. Finally, we showed that the each of these CDKs contributes to PML degradation induced by DIP-2. Together, this study not only presents the expression features of DIP-2 in mouse brain, but also provides a linkage between DIP-2-mediated PML degradation and cell cycle-dependent regulation of PML, thus adding another aspect of proper control for the stability of tumor suppressor PML protein.
Subjects
brain
BTB-kelch
CDK
DIP-2
PML
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