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Review
. 2013 Apr 11;121(15):2845-53.
doi: 10.1182/blood-2012-11-292037. Epub 2013 Feb 8.

Role of LRF/Pokemon in lineage fate decisions

Andrea Lunardi  1 , Jlenia Guarnerio, Guocan Wang, Takahiro Maeda, Pier Paolo Pandolfi
Affiliations
Review

Role of LRF/Pokemon in lineage fate decisions

Andrea Lunardi et al. Blood. .

Abstract

In the human genome, 43 different genes are found that encode proteins belonging to the family of the POK (poxvirus and zinc finger and Krüppel)/ZBTB (zinc finger and broad complex, tramtrack, and bric à brac) factors. Generally considered transcriptional repressors, several of these genes play fundamental roles in cell lineage fate decision in various tissues, programming specific tasks throughout the life of the organism. Here, we focus on functions of leukemia/lymphoma-related factor/POK erythroid myeloid ontogenic factor, which is probably one of the most exciting and yet enigmatic members of the POK/ZBTB family.

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Figures

Figure 1
Figure 1
LRF protein structure, modifications, and interactions. (A) LRF protein domains and posttranslational modifications. (B) LRF protein interactions.
Figure 2
Figure 2
LRF in the hematopoietic cell lineages. LRF regulates hematopoiesis by playing specific roles in different cell lineages.
Figure 3
Figure 3
LRF in the erythrocytes lineage. (A) LRF promotes erythrocyte differentiation. (B) GATA1-dependent LRF upregulation drives a potent antiapoptotic activity during the late stage of erythroblast differentiation through (C) BIM transcriptional repression.
Figure 4
Figure 4
LRF roles in lymphoid differentiation. LRF promotes B-cell lineage by repressing Notch activity in early lymphoid precursors, whereas LRF regulates mature B-cell lineage fate and GC formation through distinct mechanisms.
Figure 5
Figure 5
Cell nonautonomous function of LRF in LT-HSCs differentiation. (A) Cell nonautonomous inhibition of the Notch pathway and block of LT-HSCs differentiation through (B) LRF-dependent downregulation of Dll4 in the erythroblastic islands.
Figure 6
Figure 6
LRF role in osteoclastogenesis. (A-B) LRF transcriptional inhibition of Nfatc1 during the early stage of osteoclast differentiation. (A-C) LRF is an essential cofactor for NFATc1 transcriptional activity during osteoclast terminal differentiation.
Figure 7
Figure 7
LRF in tumorigenesis. Examples of context-dependent and dose-dependent oncogenic or oncosuppressive functions of LRF.
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