p53 regulates katanin-p60 promoter in HCT 116 cells


Kirimtay K., Selcuk E. , Kelle D., Erman B., Karabay A.

GENE, cilt.727, 2020 (SCI İndekslerine Giren Dergi)

Özet

Tumor suppressor protein p53, which functions in the cell cycle, apoptosis and neuronal differentiation via transcriptional regulations of target genes or interactions with several proteins, has been associated with neurite outgrowth through microtubule re-organization. We previously demonstrated in neurons that upon p53 induction, the level of microtubule severing protein Katanin-p60 increases, indicating that p53 might be a transcriptional regulator of the KATNA1 gene encoding Katanin-p60. In this context, we firstly elucidated the activity of KATNA1 regulatory regions and endogenous KATNA1 mRNA levels in the presence or absence of p53 using HCT 116 WT and HCT 116 p53 (-/-) cells. Next, we demonstrated the binding of p53 to the KATNA1 promoter and then investigated the role of p53 on KATNA1 gene expression by ascertaining KATNA1 mRNA and Katanin-p60 protein levels upon p53 overexpression and activation in both cells. Moreover, we showed changes in microtubule network upon increased Katanin-p60 level due to p53 overexpression. Also, the changes in KATNA1 mRNA and Katanin-p60 protein levels upon p53 knockdown were investigated. Our results indicate that p53 is an activator of KATNA1 gene expression and we show that both p53 and Katanin-p60 expression have strict regulations and are maintained at balanced levels as they are vital proteins to orchestrate either survival and apoptosis or differentiation.