zinc finger protein Gfi-1b (growth factor independent protein 1B, potential regulator of CDKN1A translocated in CML, GFI1B)

Function: - proto-oncogenic transcriptional regulator necessary for development & differentiation of erythroid & megakaryocytic lineages. - transcriptional repressor or activator depending on both promoter & cell type context - represses promoter activity of SOCS1 & SOCS3 & thus, may regulate cytokine signaling pathways - cooperates with GATA1 to repress target gene transcription, including apoptosis regulator BCL2L1 - GFI1B silencing in leukemic cell lines markedly increase apoptosis - inhibits down-regulation of MYC & MYB as well as the cyclin-dependent kinase inhibitor CDKN1A/P21WAF1 in IL6-treated myelomonocytic cells - represses expression of GATA3 in T-cell lymphomas & inhibits GATA1-mediated transcription; as GATA1 also mediates erythroid GFI1B transcription, both GATA1 & GFI1B participate in a feedback regulatory pathway controlling the expression of GFI1B gene in erythroid cells - suppresses GATA1-mediated stimulation of GFI1B promoter through protein interaction - binds to gamma-satellite DNA & to its own promoter, auto-repressing its own expression - alters histone methylation by recruiting histone methyltransferase to target genes promoters - plays a role in heterochromatin formation - forms a complex with GATA1 - interacts with histone methyltransferases EHMT2 & SUV39H1 Structure: - zinc finger domains are essential for erythroid expansion & acts as an activation domain whereas non finger domain serves as repression domain (putative) - contains 6 C2H2-type zinc fingers Compartment: nucleus Alternative splicing: named isoforms=2 Expression: - expressed in bone marrow & fetal liver - also detectable in fetal spleen, fetal thymus, & testes - detected in hematopoietic stem cells, erythroblasts, & megakaryocytes - induced by GATA1 which binds to GFI1B promoter in cooperation with the transcription factor NFYA. Pathology: - overexpressed in bone marrow of patients with erythroleukemia & megakaryocytic leukemia as well as in their corresponding leukemic cell lines - markedly repressed in severe aplastic anemia - target gene of transcription factor E2-alpha/TCF3 that promotes growth arrest & apoptosis in lymphomas

General

C2H2 type zinc finger protein nuclear protein

Properties

SIZE: entity length = 330 aa MW = 37 kD COMPARTMENT: cell nucleus MOTIF: Mediates repression of transcription {1-20} Zn finger C2H2-type SITE: 163-186 EFFECTOR-BOUND: Zn+2 Mediates interaction with GATA1 {164-330} MOTIF: Zn finger C2H2-type SITE: 192-214 EFFECTOR-BOUND: Zn+2 Zn finger C2H2-type SITE: 220-242 EFFECTOR-BOUND: Zn+2 Zn finger C2H2-type SITE: 248-270 EFFECTOR-BOUND: Zn+2 Ser phosphorylation site {S261} Zn finger C2H2-type SITE: 276-298 EFFECTOR-BOUND: Zn+2 Zn finger C2H2-type SITE: 304-327 EFFECTOR-BOUND: Zn+2

Database Correlations

OMIM 604383 UniProt Q5VTD9 Pfam PF00096

References

UniProt :accession Q5VTD9