eLife: Studies have found that destroying the interoperability between MYC and HCF-1 can ablate tumors

MYC cancer proteins are the main driver of most human cancers, causing nearly one-third of cancer-related deaths each year.
it can act as both transcription activation factor and deterrent factor, regulating cell cycle and apoptosis, protein synthesis and metabolism, genomic stability and angiogenesy by combining with other cofactors.
because of the difficulty of targeting MYC in current treatments and research methods, inhibiting the inter-effect of other proteins and MYC is considered the direction of the current development of new anticancer therapies.
recently, researchers from Vanderburg University in the United States published in eLife the results of a study entitled MYC regulations ribosome biogenesis and mitochondrial gene expression programs through its interaction with with host cell factor-1, identifying HCF-1 1 is the key cofactor of MYC, and the mutual regulation of the two affects cell growth, amino acid metabolism, nuclear glycosome biological occurrence and mitochondrial function, and the destruction of this interaction will promote the rapid and continuous retreat of tumors in the body, which can be used as the focus of the development of new anti-MYC therapy.
host cytokine HCF-1 is a chromatin-related protein necessary in cell proliferation and can act as a cofactor of cell transcription factor in uninfed cells.
researchers first introduced many mutations in myC's HBM sequence to analyze their interoperability with HCF-1 and found that myC-HCF-1 interactions were disrupted after all four residuals of the HBM sequence mutated to alanine (4A).
the destruction of the ability to obtain and lose systems so interoperability to study the interaction between MYC and HCF-1 have on cells? After further testing of Burkitt lymphoma (bl) cells, the researchers found that the interoperability of MYC-HCF-1 promoted glutamine dependence and rapid proliferation of these BL cells in culture, which is also the capability of myC alone;
After transcriptional group analysis of cells in different states of MYC-HCF-1 interactions, the researchers found that 4A mutations led to reduced gene expression associated with nuclear glycosome organisms, tRNA metabolism, and mitochondrial substations, suggesting that MYC-HCF-1 interactions may play an important role in gene expression that promotes the occurrence of nuclear glycosome organisms and maintains mitochondrial function.
ChIP-Seq direct transcription target identification results show that most HCF-1N binding site on chromatin in BL cells is also combined with MYC, mainly located in the HCF-1-related mitochondrial envelope, cell cycle and CYP complex biogenesis and other functions of the gene initiator near the end, and nearly one-third of the gene expression is affected by 4A mutation.
also suggests that genes that occur in nuclear glycogens and are connected to mitochondrials are direct targets for MYC-HCF-1 interactions and are positively regulated by their interactions.
MYC-HCF-1 interactions affect the expression of genes involved in nuclear glycosome biogenesis and mitochondrial pathways, the researchers also found that the interactions between MYC and HCF-1 did not affect the ability of the two proteins to bind to their chromatin binding points.
Because MYC's ability to regulate the occurrence of cystic and mitochondrial organisms is at the heart of its tumor-like nature, the researchers speculate that disrupting its interoperability with HCF-1 may affect the ability of BL cells to build and maintain tumors.
By testing the condition of fibroblast tumors in mice with 4A MYC mutants, the researchers found that myC's interaction with HCF-1 was critical to maintaining tumors, and with high levels of apoptosis, mutual destruction caused by 4A mutations also contributed to the rapid and sustained disappearance of tumors in mice, resulting in a significant increase in survival.
, which requires MYC-HCF-1 interactions for tumor implantation and maintenance, say the study has shown exciting results in mouse trials, but is a long way from being used in the treatment of human cancer.