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Regulation of the DNA binding of p53 by its interaction with protein kinase CK2
A Prowald1, N Schuster, M Montenarh
1Department of Medical Biochemistry, University of the Saarland, Homburg, Germany.
Abstract:
Some of the numerous functions of the growth suppressor protein p53 are regulated by its interaction with viral and cellular proteins. C-terminal sequences of p53 are implicated in binding to the regulatory beta-subunit of protein kinase CK2. Using a p53-specific DNA binding element we found that the beta-subunit of CK2 inhibited the DNA binding of p53 whereas the alpha-subunit had no influence. The CK2 holoenzyme consisting of two alpha- and two beta-subunits led to a supershift in DNA binding of p53 similar to the p53-specific monoclonal antibody PAb421 as well as the C-terminus of p53. Thus, our results showed an individual role of the free beta-subunit of CK2 on the DNA binding activity of p53.
Insights
The beta-subunit of protein kinase CK2 inhibits the DNA binding of the growth suppressor protein p53. This finding reveals a specific role for the CK2 beta-subunit in regulating p53 DNA binding activity.
Area of Science:
- Molecular Biology
- Cellular Biology
- Protein Interactions
Background:
- The tumor suppressor protein p53 has diverse functions, often modulated by protein interactions.
- The C-terminal region of p53 is known to interact with cellular proteins, including subunits of protein kinase CK2.
Purpose of the Study:
- To investigate the specific role of protein kinase CK2 (CK2) subunits in regulating the DNA binding activity of the p53 protein.
Main Methods:
- Utilized a p53-specific DNA binding element to assess DNA binding in the presence of CK2 subunits.
- Compared the effects of the free CK2 beta-subunit, the alpha-subunit, and the CK2 holoenzyme on p53 DNA binding.
Main Results:
- The free beta-subunit of CK2 significantly inhibited the DNA binding of p53.
- The alpha-subunit of CK2 did not influence p53 DNA binding.
- The complete CK2 holoenzyme induced a supershift in p53 DNA binding, comparable to the p53-specific antibody PAb421.
Conclusions:
- The beta-subunit of CK2 plays an individual and inhibitory role in modulating the DNA binding activity of p53.
- These findings highlight a specific regulatory mechanism of p53 function by CK2.