Publications by authors named "M Taipale"
Article Synopsis
- * A study using a human mutation library identified certain unstable mutations that predominantly rely on the ubiquitin proteasome system for degradation and found that the co-chaperones DNAJA1 and DNAJA2 interact significantly with one of the mutated proteins.
- * DNAJA2 plays a dual role: it stabilizes various normal proteins and specifically helps reduce the breakdown of some mutated proteins, highlighting how the protein quality control mechanisms adapt to handle misfolded proteins in the cytosol.
Article Synopsis
- Triple-negative breast cancer (TNBC) is a severe and recurrent type of breast cancer, making it challenging to manage.
- Researchers analyzed circulating micro-RNAs (cmiRNAs) from serum samples of 33 TNBC patients to identify differences between recurrent and non-recurrent cases, discovering ten differentially expressed cmiRNAs.
- Three specific cmiRNAs (miR-21-5p, miR-16-5p, and miR-26b-5p) were linked to recurrence-free survival, suggesting they could serve as biomarkers for assessing recurrence risk in TNBC.
Article Synopsis
- Widespread sequencing has identified thousands of missense variants linked to diseases, creating a challenge in assessing their functional impact at scale.
- A new high-throughput imaging platform was developed to evaluate the effects of 3,448 missense variants across over 1,000 genes, revealing that mislocalization of proteins is a frequent outcome.
- Mislocalization affects about one-sixth of pathogenic variants and is mainly caused by issues with protein stability and membrane insertion, which can influence disease severity and help interpret uncertain variants.
Targeted intracellular delivery of therapeutic proteins remains a significant unmet challenge in biotechnology. A promising approach is to leverage the intrinsic capabilities of bacterial toxins like diphtheria toxin (DT) to deliver a potent cytotoxic enzyme into cells with an associated membrane translocation moiety. Despite showing promising clinical efficacy, widespread deployment of DT-based therapeutics is complicated by the prevalence of pre-existing antibodies in the general population arising from childhood DT toxoid vaccinations, which impact the exposure, efficacy, and safety of these potent molecules.
View Article and Find Full Text PDFHeat Shock Factor 1 (HSF1) is best known as the master transcriptional regulator of the heat-shock response (HSR), a conserved adaptive mechanism critical for protein homeostasis (proteostasis). Combining a genome-wide RNAi library with an HSR reporter, we identified Jumonji domain-containing protein 6 (JMJD6) as an essential mediator of HSF1 activity. In follow-up studies, we found that JMJD6 is itself a noncanonical transcriptional target of HSF1 which acts as a critical regulator of proteostasis.
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