Lessons Learned: HIV Points the Way Towards Precision Treatment of Mixed-Lineage Leukemia.
Protein-protein interactions are involved in most if not all pathogenic and pathophysiological processes and represent attractive therapeutic targets. Extensive biological and clinical research efforts have led to the identification and validation of several cellular hubs that are crucially involved in disease pathogenesis. An interesting example of such a hub is the lens epithelium-derived growth factor (LEDGF/p75), a protein that tethers multiple unrelated proteins and protein complexes to the chromatin. Its chromatin-tethering ability is linked to at least two unrelated diseases-HIV infection and MLL-rearranged acute leukemia. In this review we discuss recent progress in our understanding of the interaction of LEDGF/p75 with its binding partners and focus on the first steps towards therapies targeting protein-protein interactions of LEDGF/p75.
KU Leuven, Laboratory for Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium; Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic (ASCR), v.v.i, Laboratory of Structural Biology, Prague, Czech Republic.
Katerina
K
Cermakova
KU Leuven, Laboratory for Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium.
Caroline
C
Weydert
KU Leuven, Laboratory for Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium.
Frauke
F
Christ
KU Leuven, Laboratory for Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium.
Jan
J
De Rijck
KU Leuven, Laboratory for Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium. Electronic address: Zeger.Debyser@kuleuven.be.
Zeger
Z
Debyser
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000075202:Contraindications; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D058990:Molecular Targeted Therapy; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics / Q000378:metabolism; D057285:Precision Medicine / Q000379:methods*; D054730:Protein Interaction Domains and Motifs; D054852:Small Molecule Libraries / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C504649:PSIP1 protein, human; D054852:Small Molecule Libraries; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase
HIV; LEDGF/p75; MLL; integration; protein–protein interaction; targeted therapies