TATA-binding Protein (TBP)-like Protein Is Engaged in Etoposide-induced Apoptosis through Transcriptional Activation of Human TAp63 Gene.
Accumulating evidence indicates that TBP (TATA-binding protein)-like protein (TLP) contributes to the regulation of stress-mediated cell cycle checkpoint and apoptotic pathways, although its physiological target genes have remained elusive. In the present study, we have demonstrated that human TAp63 is one of the direct transcriptional target genes of TLP. Enforced expression of TLP results in the transcriptional induction of the endogenous TAp63, but not of the other p53 family members such as TAp73 and p53. Consistent with these results, small interference RNA-mediated knockdown led to a significant down-regulation of the endogenous TAp63. Luciferase reporter assay and chromatin immunoprecipitation analysis revealed that the genomic region located at positions -487 to -29, where +1 represents the transcriptional initiation site of TAp63, is required for TLP-dependent transcriptional activation of TAp63 and also TLP is efficiently recruited onto this region. Additionally, cells treated with anti-cancer drug etoposide underwent apoptosis in association with the transcriptional enhancement of TAp63 in a p53-independent manner, and the knockdown of the endogenous TLP reduced etoposide-induced apoptosis through repression of TAp63 expression. Taken together, our present study identifies a TLP-TAp63 pathway that is further implicated in stress-induced apoptosis.
Graduate School of Science, Chiba University, 1-33 Yayoicho, Inage-ku, Chiba 263-8522.
Yusuke
Y
Suenaga
Toshinori
T
Ozaki
Yuji
Y
Tanaka
Youquan
Y
Bu
Takehiko
T
Kamijo
Takeshi
T
Tokuhisa
Akira
A
Nakagawara
Taka-Aki
TA
Tamura
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002645:Chickens; D005047:Etoposide / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D035182:TATA Box Binding Protein-Like Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects* / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
D000972:Antineoplastic Agents, Phytogenic; D035182:TATA Box Binding Protein-Like Proteins; C495901:TP53 protein, human; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D005047:Etoposide