Biomedical subjects

Li-Huei Tsai

Publications and source records attributed to Li-Huei Tsai.

39 records · Page 3Linked to original sources

PubMed2002

Colocalization and fluorescence resonance energy transfer between cdk5 and AT8 suggests a close association in pre-neurofibrillary tangles and neurofibrillary tangles.

Cyclin-dependent kinase 5 (cdk5) is a serine/threonine kinase that, when activated, induces neurite outgrowth. Recent in vitro studies have shown that cdk5 phosphorylates tau at serine 199, serine 202, and threonine 205 and that p25, an activator of cdk5, is increased in Alzheimer disease (AD). Since tau is hyperphosphorylated at these sites in neurofibrillary tangles, we examined brain tissue from patients with AD and normal elderly control cases to determine whether cdk5 and these phosphoepitopes colocalize in neurofibrillary tangles. Adjacent temporal lobe sections were double immunostained with a polyclonal anti-cdk5 and monoclonal AT8 (which recognizes phosphorylated serine 199, serine 202, and threonine 205 in tau) antibodies. A subset of AT8 phosphotau-positive neurons was immunoreactive for cdk5 in entorhinal (area 28) and perirhinal (area 35) cortices and CA1 of the hippocampus. We assessed the ratio of cdk5-positive cells to AT8-positive cells and found that there is a higher degree of colocalization in pre-neurofibrillary tangles as opposed to intraneuronal and extraneuronal neurofibrillary tangles. We further examined colocalization using fluorescence resonance energy transfer. This suggests a close, stable intermolecular association between cdk5 and phosphorylated tau, consistent with phosphorylation of tau by cdk5 in AD brain.

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PubMed2001

GC box-binding transcription factors control the neuronal specific transcription of the cyclin-dependent kinase 5 regulator p35.

Cyclin-dependent kinase 5 (cdk5)/p35 kinase activity is highest in post-mitotic neurons of the central nervous system and is critical for development and function of the brain. The neuronal specific activity of the cdk5/p35 kinase is achieved through the regulated expression of p35 mRNA. We have identified a small 200-bp fragment of the p35 promoter that is sufficient for high levels of neuronal specific expression. Mutational analysis of this TATA-less promoter has identified a 17-bp GC-rich element, present twice, that is both required for promoter activity and sufficient for neuronal specific transcription. A GC box within the 17-bp element is critical for both promoter activity and protein-DNA complex formation. The related transcription factors Sp1, Sp3, and Sp4 constitute most of the GC box DNA binding activity in neurons. We have found that both the relative contribution of the Sp family proteins to GC box binding and the transcriptional activity of these proteins is regulated during neuronal differentiation. Thus, our data show that the GC box-binding Sp proteins contribute to the regulation of p35 expression in neurons, suggesting changes in the Sp transcription factors level and activity may contribute to cell type-specific expression of many genes in the central nervous system.

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PubMedDate not supplied

Cyclin-dependent kinase 5 and neuronal migration in the neocortex.

The cyclin-dependent kinase 5 (Cdk5) plays an important role in the proper establishment of neocortical layers. Over the past several years, key molecular targets of Cdk5 have been identified that show intriguing connections to the adhesional and cytoskeletal components of cell movement. This molecular knowledge about Cdk5 signaling has begun to translate into an understanding of how Cdk5 regulates the cellular physiology of neocortical layer formation. Together with recent progress on the signaling relationship between Cdk5 and Reelin, the other key protein involved in neocortical layer formation, and their relationship to migration modes, research on understanding neocortical layer formation has arrived at a most promising crossroad.

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