Interaction between human papillomavirus type 5 E2 and polo‐like kinase 1

The E2 protein of the papillomavirus plays an essential role in the viral life cycle. Through a yeast two‐hybrid screening, human polo‐like kinase 1 was found to interact with human papillomavirus type 5 E2. Further characterization identified that the domains responsible for the interaction are the transactivation domain of HPV‐5 E2 and the sequence between the kinase and the polo box domains of Plk1. In vivo, Plk1 and HPV‐5 E2 are colocalized at the nuclear speckles. In the skin epithelium not infected with epidermodysplasia verruciformis associated HPVs, Plk1 is expressed in the stratum basale, indicating that the Plk1–HPV‐5 E2 interaction likely occurs in the keratinocytes at the basal layer of the epithelium upon infection of HPV‐5. Both HPV‐5 E2 and Plk1 also interact with the E2 binding domain of Brd4. The E2 binding domain of Brd4 is phosphorylated by Plk1 in vitro, and this phosphorylation event is blocked by the presence of HPV‐5 E2. Hence, these findings suggest the possibility that the cellular function of Brd4 is de‐regulated by forming a complex with HPV‐5 E2 in the infected epithelial cells. J. Med. Virol. 81:536–544, 2009. © 2009 Wiley‐Liss, Inc.     

Regulation of neuron survival and death by p130 and associated chromatin modifiers

E2F-mediated gene repression plays a key role in regulation of neuron survival and death. However, the key molecules involved in such regulation and the mechanisms by which they respond to apoptotic stimuli are largely unknown. Here we show that p130 is the predominant Rb family member associated with E2F in neurons, that its major partner for repression of pro-apoptotic genes is E2F4, and that the p130-E2F4 complex recruits the chromatin modifiers HDAC1 and Suv39H1 to promote gene silencing and neuron survival. Apoptotic stimuli induce neuron death by sequentially causing p130 hyperphosphorylation, dissociation of p130-E2F4-Suv39H1-HDAC complexes, altered modification of H3 histone and gene derepression. Experimental suppression of such events blocks neuron death while interference with the synthesis of E2F4 or p130, or with the interaction of E2F4-p130 with chromatin modifiers, induces neuron death. Thus, neuron survival and death are dependent on the integrity of E2F4-p130-HDAC/Suv39H1 complexes.