Publications by authors named "Kristina Zaprazna"
Article Synopsis
- Activation-induced cytidine deaminase (AID) is a crucial enzyme involved in immune processes, and its abnormal activity is linked to various cancers, including chronic lymphocytic leukemia (CLL).
- In a study of 149 CLL patients, researchers quantified different AID variants and found a connection between higher AID levels and trisomy of chromosome 12, a genetic abnormality.
- Functional assessments showed that the altered AID splice variants had reduced activity for important processes like somatic hypermutation and DNA break induction, and modeling studies suggested structural changes leading to their loss of function.
Article Synopsis
- - AID is essential for immune system processes like somatic hypermutation and class switch recombination, as it deaminates cytosine to create mutations or DNA breaks that aid in antibody diversity.
- - The regulation of AID levels is important because imbalances can lead to unwanted mutations and diseases like lymphoma; YY1 is a transcription factor that influences AID levels and activity.
- - In experiments with mouse models, removing YY1 resulted in lower AID levels and mutations, indicating that YY1 may help keep AID stable in the nucleus by preventing its ubiquitination.
Treatment options for TP53-mutated lymphoid tumors are very limited. In experimental models, TP53-mutated lymphomas were sensitive to direct inhibition of checkpoint kinase 1 (Chk1), a pivotal regulator of replication. We initially tested the potential of the highly specific Chk1 inhibitor SCH900776 to synergize with nucleoside analogs (NAs) fludarabine, cytarabine and gemcitabine in cell lines derived from B-cell malignancies.
View Article and Find Full Text PDFMicroRNA (miRNA) expression is deregulated in many tumors including chronic lymphocytic leukemia (CLL). Although the particular mechanism(s) responsible for their aberrant expression is not well characterized, the presence of mutations and single-nucleotide polymorphisms (SNPs) in miRNA genes, possibly affecting their secondary structure and expression, has been described. In CLL; however, the impact and frequency of such variations have yet to be elucidated.
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- Conditional knock-out of the YY1 protein in pro-B cells leads to their developmental arrest and hinders the rearrangement of immunoglobulin genes necessary for efficient immune responses.
- A mutant version of YY1 lacking the REPO domain was unable to support B-cell lineage development, resulting in fewer B cells despite normal IgH rearrangement.
- The REPO domain interacts with proteins from the condensin and cohesin complexes, indicating that YY1, along with these proteins, plays a crucial role in shaping the Igκ locus for effective gene rearrangement.
Article Synopsis
- YY1 is a transcription factor crucial for early B cell development, and its absence leads to a halt in the formation of pro-B cells in mice.
- Increasing YY1 levels in mouse bone marrow results in poor progression through B cell stages but does not affect myeloid lineage cells.
- The elevation of YY1 expression causes apoptosis in B cell lines and reduces anti-apoptotic gene expression, suggesting that modulating YY1 could help treat B cell cancers while protecting hematopoietic stem cells.
Article Synopsis
- Activation-induced deaminase (AID) is essential for antibody maturation, specifically in processes like class switch recombination (CSR) and somatic hypermutation (SHM).
- The transcription factor YY1, important for early B cell development, was found to be crucial for CSR in activated splenic B cells by maintaining the stability of AID in the nucleus.
- YY1 knockout did not affect cell proliferation or the transcription of specific genes, but it disrupted the accumulation of nuclear AID, revealing a new role for YY1 in controlling AID protein levels during CSR.
Yin Yang 1 (YY1) is a ubiquitously expressed transcription factor that performs numerous functions including transcriptional regulation, cell growth control, apoptosis, large-scale chromosomal dynamics, and X-chromosome inactivation. YY1 clearly is able to control cell functions, including proliferation, by acting as a transcription factor either to activate or repress specific genes. Based on its ability to regulate cell growth control genes, it has been argued that YY1 can function as an oncogene that initiates oncogenesis.
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- BCL6 is essential for the formation of germinal centers and functions as a transcriptional repressor by binding to specific DNA sequences and interacting with other proteins.
- The research showed that BCL6 inhibits the activity of immunoglobulin kappa intron and 3' enhancers, specifically affecting the PU.1 binding site at the Igkappa 3' enhancer.
- It was found that BCL6 works together with PU.1 to regulate gene expression, with knockdown of BCL6 leading to increased expression of several genes, indicating BCL6's role in gene repression.