H2020Индивидуална стипендия2021–2025

SpinSAC · hSpindly, a new regulatory protein of the SAC mechanism and its implication in tumour therapy

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2021-09-01 → 2025-02-16
Финансиране от ЕС: 259 399 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Протеинът hSpindly и неговата роля при контрола на деленето на клетките се анализират чрез промяна в химичния му състав. Разбирането на този механизъм помага да се разбере защо някои туморни клетки стават устойчиви на химиотерапия.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

hSpindly, a new regulatory protein of the SAC mechanism and its implication in tumour therapy

During mitosis a surveillance system, known as the spindle assembly checkpoint (SAC), is crucial to make sure that the cell does not separate its sister chromatids until all the chromosomes are correctly attached to spindle microtubules and bi-oriented. Nowadays, one of the more important strategy used for the cancer treatment is the inhibition of the microtubule dynamic to activate the SAC by the addition of antimitotic drugs. At the end, the activation of SAC for a long period of time would provoke the cell death. However, many tumor cells exhibit defects in SAC functionality, leading chromosomal instability (CIN) and resistance to the treatment. For this reason, it is becoming extremely useful to seek new proteins which are implicated directly to SAC functionality. This project has been focused on the study of hSpindly, a protein whose role in SAC regulation had not been clearly defined. Preliminary evidence suggested that hSpindly may participate in SAC activation through a mechanism independent of the stripping pathway. However, the exact mode of action remained completely unknown at the start of this fellowship. Since hSpindly is highly phosphorylated in mitosis, we hypothesized that its phosphorylation pattern could play a critical role in modulating its function. The overall objectives of the project were: • To identify the phosphorylation pattern of hSpindly during mitosis and production of point mutants. • To analyze the functions of the hSpindly phosphorylations in mitosis and the role of these phosphorylations in the cell response to anti-mitotic drugs. This project has revealed the regulatory role of hSpindly in the SAC pathway and identified threonine 552 as a critical phosphorylation site affecting its function. These findings enhance our understanding of drug resistance in cancer and pave the way for the development of personalized therapies, new biomarkers, and targeted treatments with relevance for both research and clinical applications.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

During mitosis a sophisticated surveillance system, known as the spindle assembly checkpoint (SAC), is crucial to make sure that the cell does not separate its sister chromatids until all the chromosomes are correctly attached to spindle microtubules and bi-oriented.Nowadays, one of the more important strategy used for the cancer treatment is the inhibition of the microtubule dynamic to activate the SAC by the addition of anti-mitotic drugs. At the end, the activation of SAC for a long period provokes the cell death, compromising the tumour cell proliferation. Nonetheless, there are tumour cells, which are affected in SAC activity showing a reduction in the efficiency of this treatment. For this reason, it is becoming extremely useful to seek new proteins which are implicated directly to SAC functionality.This project will be focused on the study of hSpindly as a new protein implicated in SAC regulation independently of the stripping pathway. hSpindly has a role in the SAC mechanism but how it works is absolutely unknown. hSpindly is highly phosphorylated in mitosis so, finding the residues which are phosphorylated in this cell cycle phase, will allow us to know not only the role of these phosphorylations in SAC but also its implication in the cell response in the presence of antimitotic drugs. For this, we will use several approaches and state of the art techniques as confocal microscopy and the CRISPR/Cas9 nickase system. This study will contribute with relevant results in basic and clinical research. The knowledge of the hSpindly function might reveal new therapeutic targets for the treatment of the tumours more resistant to anti-mitotic drugs. Additionally, it would be possible to get phosphospecific antibodies of key residues in the hSpindly function, which could be used as tumour marker in the future.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSIDAD DE SEVILLA · SevillaКоординаторИспания