Disease relevance of Pcgf2

• Complementation with CITED2-expressing retrovirus enhanced proliferation, induced Bmi1/Mel18 expression, and decreased INK4a/ARF expression [1].
• EXPERIMENTAL DESIGN: We measure the expression of PcG members Bmi-1, Mel-18, and Hpc-2 and their potential targets by reverse transcription-PCR, immunostaining, and Western blotting in a series of 134 breast carcinomas and correlate the data with several clinical-pathologic variables of the tumors [2].
• Mutation analysis of the mel-18 gene that shows decreased expression in human breast cancer cell lines [3].

High impact information on Pcgf2

• The bmi-1 and mel-18 gene products define a new family of DNA-binding proteins involved in cell proliferation and tumorigenesis [4].
• These alterations are enhanced by Zfp144 mutation but repressed by Mll mutation (a trithorax-group gene) [5].
• We therefore propose that mel-18 negatively regulates the cell cycle through a c-myc/cdc25 cascade [6].
• Strikingly, the axial skeleton and lymphoid phenotypes are identical in both mel-18 and bmi-1 mutants, indicating that the Mel-18 and Bmi-1 gene products might act in the same genetic cascade [7].
• In this study, the severe combined immunodeficiency observed in mel-18 mutant mice is correlated with the impaired mitotic response of lymphocyte precursors upon interleukin-7 stimulation [7].

Biological context of Pcgf2

• We also demonstrate that mel-18 has tumor suppressor activity, in contrast to bmi-1, which has been defined as a proto-oncogene [8].
• Overexpression of mel-18 in mice results in cell cycle arrest of B cells upon B cell receptor stimulation with downregulation of c-myc [6].
• Mel-18 protein mediates a transcriptional repression via direct binding to specific DNA sequences [9].
• In addition, we demonstrate that Mel18 and Bmi1, although essential for maintenance of the appropriate expression domains of Hox cluster genes, are not required for the initial establishment of Hox gene expression [10].
• The percentage in G0 phase HSCs (lin(-)flk2(-)c-Kit(+)Sca1+ cells) was increased in mel-18(-/-) mice and decreased in mel-18 tg mice [11].

Anatomical context of Pcgf2

• Our results provide genetic evidence that Cited2 controls the expression of INK4a/ARF and fibroblast proliferation, at least in part via the polycomb-group genes Bmi1 and Mel18 [1].
• In this report we demonstrate that the loss of the PcG gene mel-18 impairs the expansion of the most immature T progenitor cells at a stage before the rearrangement of the TCR beta-chain gene in vivo and in vitro [12].
• Here, we demonstrate that mel-18 negatively regulates the self-renewal activity of hematopoietic stem cells (HSCs) [11].
• Mice lacking the gene mel-18, a member of the mammalian Polycomb group genes, displayed impaired thymic T cell development [13].
• Here, we show in vitro by pull-down assays and in vivo in transiently transfected COS-7 cells that Mel-18 forms homodimers [14].

Regulatory relationships of Pcgf2

• RESULTS: The Hoxb4 gene was highly expressed in HSCs derived from mel-18(-/-) mice [11].

Other interactions of Pcgf2

• Collectively, these data indicate that mel-18 contributes to the maintenance of the active state of the Hes-1 gene as a cellular memory system, thereby supporting the expansion of early T progenitors [12].
• However, expression of the other PcG members Mel-18 and Hpc-2 correlated with the cell cycle regulators [2].
• CONCLUSION: Loss or knockdown of mel-18 leads to the expression of Hoxb4, an increase in the proportion of HSCs in G0 phase, and the subsequent promotion of HSC self-renewal [11].
• Chemokine-mediated thymopoiesis is regulated by a mammalian Polycomb group gene, mel-18 [13].

Analytical, diagnostic and therapeutic context of Pcgf2

• The expression levels of mel-18 and Hoxb4 were measured by quantitative real-time reverse transcription polymerase chain reaction [11].

References