Modulation of Krüppel-like factors (KLFs) interaction with their binding partners in cancers through acetylation and phosphorylation.

Kanupriya Jha, Amit Kumar, Kartik Bhatnagar, Anupam Patra, Neel Sarovar Bhavesh, Bipin Singh, Sarika Chaudhary

Journal: Biochimica et biophysica acta. Gene regulatory mechanisms 2024;1867(1):195003

PMID: 37992989

Full Text on Elsevier Science View on PubMed

Abstract

Post-translational modifications (PTMs) of transcription factors regulate transcriptional activity and play a key role in essentially all biological processes and generate indispensable insight towards biological function including activity state, subcellular localization, protein solubility, protein folding, substrate trafficking, and protein-protein interactions. Amino acids modified chemically via PTMs, function as molecular switches and affect the protein function and characterization and increase the proteome complexity. Krüppel-like transcription factors (KLFs) control essential cellular processes including proliferation, differentiation, migration, programmed cell death and various cancer-relevant processes. We investigated the interactions of KLF group-2 members with their binding partners to assess the role of acetylation and phosphorylation in KLFs on their binding affinity. It was observed that acetylation and phosphorylation at different positions in KLFs have a variable effect on binding with specific partners. KLF2-EP300, KLF4-SP1, KLF6-ATF3, KLF6-JUN, and KLF7-JUN show stabilization upon acetylation or phosphorylation at variable positions. On the other hand, KLF4-CBP, KLF4-EP300, KLF5-CBP, KLF5-WWP1, KLF6-SP1, and KLF7-ATF3 show stabilization or destabilization due to acetylation or phosphorylation at variable positions in KLFs. This provides a molecular explanation of the experimentally observed dual role of KLF group-2 members as a suppressor or activator of cancers in a PTM-dependent manner.

Address: Department of Biotechnology, School of Engineering and Applied Sciences, Bennett University, Plot Nos. 8-11, Tech Zone 2, Greater Noida, Uttar Pradesh 201310, India. Electronic address: [email protected].; Department of Biotechnology, School of Engineering and Applied Sciences, Bennett University, Plot Nos. 8-11, Tech Zone 2, Greater Noida, Uttar Pradesh 201310, India. Electronic address: [email protected].; Department of Biotechnology, School of Engineering and Applied Sciences, Bennett University, Plot Nos. 8-11, Tech Zone 2, Greater Noida, Uttar Pradesh 201310, India. Electronic address: [email protected].; Transcription Regulation Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi 110067, India. Electronic address: [email protected].; Transcription Regulation Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi 110067, India. Electronic address: [email protected].; Department of Biotechnology, School of Engineering and Applied Sciences, Bennett University, Plot Nos. 8-11, Tech Zone 2, Greater Noida, Uttar Pradesh 201310, India; Centre for Life Sciences, Mahindra University, Bahadurpally, Jeedimetla, Hyderabad, Telangana 500043, India. Electronic address: [email protected].; Department of Biotechnology, School of Engineering and Applied Sciences, Bennett University, Plot Nos. 8-11, Tech Zone 2, Greater Noida, Uttar Pradesh 201310, India. Electronic address: [email protected].

DOI: 10.1016/j.bbagrm.2023.195003

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MeSH Terms: Humans, Kruppel-Like Transcription Factors, Phosphorylation, Acetylation, Protein Processing, Post-Translational, Neoplasms, Ubiquitin-Protein Ligases