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

• Published in: Biochimica et biophysica acta. Gene regulatory mechanisms 2024-03, Vol.1867 (1), p.195003-195003, Article 195003
• Main Authors: Jha, Kanupriya, Kumar, Amit, Bhatnagar, Kartik, Patra, Anupam, Bhavesh, Neel Sarovar, Singh, Bipin, Chaudhary, Sarika
• Format: Article
• Language: English
• Subjects: Acetylation; Cancer; Humans; Kruppel-Like Transcription Factors - genetics; Krüppel-like transcription factors (KLFs); Neoplasms - genetics; Phosphorylation; Post-translational modification (PTM); Protein Processing, Post-Translational; Ubiquitin-Protein Ligases - metabolism
• ISSN: 1874-9399; 1876-4320
• DOI: 10.1016/j.bbagrm.2023.195003

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. •KLFs modulate transcription through their interaction with binding partners.•PTMs at different sites in KLFs have variable impacts.•Modulation of KLFs interaction with binding partners acts as a molecular switch.•KLFs employ PTMs to act as suppresser or promoter in Cancers.