Biology subjects

Vitre, B.

Publications and source records attributed to Vitre, B..

3 recordsLinked to original sources

bioRxiv2025

Functional regulation of the mitotic kinesin HSET by Intraflagellar Transport proteins.

HSET is a mitotic kinesin essential for centrosome clustering in cells harboring supernumerary centrosomes. Work in cellulo revealed that IntraFlagellar Transport proteins (IFT) interact with the kinesin HSET to promote efficient extra centrosome clustering and subsequent cancer cell proliferation. However, whether and how IFT proteins regulate HSET activity is unknown. Using a reconstituted in vitro system combining purified HSET and IFT proteins with TIRF microscopy approaches, we identified a minimal subcomplex made of IFT52/IFT70 directly binding to HSET. We show that this binding induces HSET oligomerization promoting the formation of processive HSET complexes. We also show that HSETs increased processivity upon IFT52/70 binding accounts for an increased ability to slide microtubules and to organize dynamic microtubule networks in vitro. Overall, this work shows that IFT proteins can directly promote the processive motility of a mitotic kinesin and provides a mechanistic explanation for the contribution of IFT proteins to efficient centrosome clustering.

cell biology↗

bioRxiv2020

Transient genomic instability drives tumorigenesis through accelerated clonal evolution

Abnormal numerical and structural chromosome content is frequently found in human cancer. To test the role of aneuploidy in tumor initiation and progression, we compared tumor development in mice with chronic chromosome instability (CIN) induced by inactivation of the spindle assembly checkpoint (produced by Mad2 deficiency) and mice with transient CIN through transiently increased expression of polo-like kinase 4 (PLK4), a master regulator of centrosome number. Tumors forming under chronic CIN gradually trended toward chromosomal gains producing a specific karyotype profile that could only be partially maintained in end-stage tumors, as determined by single-cell whole genome DNA sequencing. Short term CIN from transient PLK4 induction generated significant centrosome amplification and aneuploidy resulting in formation of aggressive T cell lymphomas in mice with heterozygous inactivation of one p53 allele or accelerated tumor development in the absence of p53. Transient CIN increased the frequency of lymphomainitiating cells (as revealed by T cell receptor sequencing) with a specific karyotype profile containing triploid chromosomes 4, 5, 14, and 15 occurring early in tumorigenesis. Overall, our evidence demonstrates that distinct CIN mechanisms drive cancers presenting specific, complex chromosomal alterations with transient CIN rapidly enhancing tumor formation by accelerating the generation of such events.

cancer biology↗

bioRxiv2019

Intraflagellar transport complex B proteins regulate the Hippo effector Yap1 during cardiogenesis

Cilia and the intraflagellar transport (IFT) proteins involved in ciliogenesis are associated with congenital heart diseases (CHD). However, the molecular links between cilia, IFT proteins and cardiogenesis are yet to be established. Using a combination of biochemistry, genetics, and live imaging methods, we show that IFT complex B proteins (Ift88, Ift54 and Ift20) modulate the Hippo pathway effector YAP1 in zebrafish and mouse. We demonstrate that this interaction is key to restrict the formation of the proepicardium and the myocardium. In cellulo experiments suggest that IFT88 and IFT20 interact with YAP1 in the cytoplasm and functionally modulates its activity, identifying a molecular link between cilia related proteins and the Hippo pathway. Taken together, our results highlight a novel role for IFT complex B proteins during cardiogenesis and shed light on an unexpected mechanism of action for ciliary proteins in YAP1 regulation. These findings provide mechanistic insights into a non-canonical role for cilia related proteins during cardiogenesis.

developmental biology↗