p73 plays a role in erythroid differentiation through GATA1 induction.
The TP73 gene gives rise to transactivation domain-p73 isoforms (TAp73) as well as DeltaNp73 variants with a truncated N terminus. Although TAp73alpha and -beta proteins are capable of inducing cell cycle arrest, apoptosis, and differentiation, DeltaNp73 acts in many cell types as a dominant-negative repressor of p53 and TAp73. It has been proposed that p73 is involved in myeloid differentiation, and its altered expression is involved in leukemic degeneration. However, there is little evidence as to which p73 variants (TA or DeltaN) are expressed during differentiation and whether specific p73 isoforms have the capacity to induce, or hinder, this differentiation in leukemia cells. In this study we identify GATA1 as a direct transcriptional target of TAp73alpha. Furthermore, TAp73alpha induces GATA1 activity, and it is required for erythroid differentiation. Additionally, we describe a functional cooperation between TAp73 and DeltaNp73 in the context of erythroid differentiation in human myeloid cells, K562 and UT-7. Moreover, the impaired expression of GATA1 and other erythroid genes in the liver of p73KO embryos, together with the moderated anemia observed in p73KO young mice, suggests a physiological role for TP73 in erythropoiesis.
Marqués-García
Fernando
F
Instituto de Biomedicina, Spain.
Ferrandiz
Nuria
N
Fernández-Alonso
Rosalía
R
González-Cano
Laura
L
Herreros-Villanueva
Marta
M
Rosa-Garrido
Manuel
M
Fernández-García
Belén
B
Vaque
José P
JP
Marqués
Margarita M
MM
Alonso
María Eugenia
ME
Segovia
José Carlos
JC
León
Javier
J
Marín
María C
MC
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000502:physiology*; D004912:Erythrocytes / Q000378:metabolism*; D004920:Erythropoiesis; D050982:GATA1 Transcription Factor / Q000096:biosynthesis / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020014:K562 Cells; D008099:Liver / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000502:physiology*; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000502:physiology*
D004268:DNA-Binding Proteins; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D009687:Nuclear Proteins; C000606460:TP73 protein, human; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C000606369:delta Np73 protein, human