6T3I

Solution structure of the HRP2 IBD

Summary for 6T3I

• Entry DOI: 10.2210/pdb6t3i/pdb
• NMR Information: BMRB: 34442
• Descriptor: Hepatoma-derived growth factor-related protein 2 (1 entity in total)
• Functional Keywords: epigenetic reader, cell cycle
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 9675.24

Authors

Veverka, V. (deposition date: 2019-10-11, release date: 2020-11-18, Last modification date: 2024-06-19)

Primary citation

Van Belle, S.,El Ashkar, S.,Cermakova, K.,Matthijssens, F.,Goossens, S.,Canella, A.,Hodges, C.H.,Christ, F.,De Rijck, J.,Van Vlierberghe, P.,Veverka, V.,Debyser, Z.
Unlike Its Paralog LEDGF/p75, HRP-2 Is Dispensable for MLL-R Leukemogenesis but Important for Leukemic Cell Survival.
Cells, 10:-, 2021

PubMed Abstract: HDGF-related protein 2 (HRP-2) is a member of the Hepatoma-Derived Growth Factor-related protein family that harbors the structured PWWP and Integrase Binding Domain, known to associate with methylated histone tails or cellular and viral proteins, respectively. Interestingly, HRP-2 is a paralog of Lens Epithelium Derived Growth Factor p75 (LEDGF/p75), which is essential for -rearranged (-r) leukemia but dispensable for hematopoiesis. Sequel to these findings, we investigated the role of HRP-2 in hematopoiesis and -r leukemia. Protein interactions were investigated by co-immunoprecipitation and validated using recombinant proteins in NMR. A systemic knockout mouse model was used to study normal hematopoiesis and MLL-ENL transformation upon the different HRP-2 genotypes. The role of HRP-2 in -r and other leukemic, human cell lines was evaluated by lentiviral-mediated miRNA targeting HRP-2. We demonstrate that MLL and HRP-2 interact through a conserved interface, although this interaction proved less dependent on menin than the MLL-LEDGF/p75 interaction. The systemic HRP-2 knockout mice only revealed an increase in neutrophils in the peripheral blood, whereas the depletion of HRP-2 in leukemic cell lines and transformed primary murine cells resulted in reduced colony formation independently of -rearrangements. In contrast, primary murine HRP-2 knockout cells were efficiently transformed by the MLL-ENL fusion, indicating that HRP-2, unlike LEDGF/p75, is dispensable for the transformation of MLL-ENL leukemogenesis but important for leukemic cell survival.

PubMed: 33477970
DOI: 10.3390/cells10010192

Experimental method

SOLUTION NMR