An inhibitory role of p53 via NF-kappaB element on the cyclin D1 gene under heat shock.

Little is known about the mechanisms underlying heat shock-mediated inhibition of cyclin D1 transcription. Here, we report that NF-kappaB site-mediated cyclin D1 transcription is inhibited by heat shock. The mRNA level of cyclin D1 decreased under heat shock (40-60%). This inhibition of transcription is promoter activity dependent and is mediated by the proximal NF-kappaB site. However, P65 overexpression did not influence the heat-inducible inhibitory pattern and heat shock did not significantly change the binding activity of p65. P53 can inhibit cyclin D1 promoter activity via an NF-kappaB site-dependent manner and its binding activity increased after heat shock. Importantly, p53 overexpression can prevent cyclin D1 promoter activation by p65. Therefore, we can deduce that p53 inhibits promoter activity under heat shock. These results reveal that the mechanism of heat shock-mediated inhibition of cyclin D1 transcription involves an NF-kappaB site. The data presented provide a new insight into the underlying heat shock inhibition of gene transcription.