Biology subjects

Sousa, P.

Publications and source records attributed to Sousa, P..

3 recordsLinked to original sources

bioRxiv2026

A large-scale analysis of the R2TP chaperone network reveals its contribution to the assembly of INO80, SRCAP and TIP60

HSP90/R2TP is an essential quaternary chaperone composed of RPAP3, PIH1D1 and the RUVBL1/RUVBL2 AAA+ ATPases. These enzymes are also part of the INO80, SRCAP and TIP60 complexes, but the relationship between these chromatin remodelers and R2TP remains unclear. Here, we performed systematic analyses of the R2TP-specific subunits RPAP3 and PIH1D1. We validated 115 interaction partners and found that many were sensitive to HSP90 or R2TP inhibition. In yeast, epistatic screens revealed functional interactions with Ino80, Swr1 (SRCAP) and NuA4 (TIP60). Consistently, human RPAP3 physically interacted with subunits of INO80, SRCAP and TIP60 and was required for the formation of these complexes. More specifically, RPAP3 enabled the co-translational association of RUVBL1/RUVBL2 with the motor subunit of these chromatin remodelers. In vitro, the client-binding domain of RUVBL1/RUVBL2 modulated their interaction with RPAP3, suggesting that client subunits displace RPAP3 from nascent complexes. Thus, R2TP is an early chaperone of TIP60, SRCAP and INO80, which leaves RUVBL1/RUVBL2 as resident scaffolding subunits.

molecular biology↗

bioRxiv2020

Single-cell analysis reveals mechanisms of plasticity of leukemia initiating cells

Leukemia initiating cells (LICs) fuel leukemic growth and spark relapse. Previously thought to be primitive and rare, the LIC state may actually be heterogeneous and dynamic, enabling evasion of therapies. Here, we use single-cell transcriptomics to track LIC multipotency within the cellular ontogeny of MLL-rearranged B-lymphoblastic leukemia (MLL-r B-ALL). Although we identify rare transcriptionally and phenotypically primitive LICs, we also observe LICs emerging from more differentiated populations with the capability to replenish the full leukemic cellular diversity. We find that activation of MYC-driven oxidative phosphorylation controls this process of facultative state conversion in LICs.

cancer biology↗

bioRxiv2019

Seminal quality and global proteomic analysis of spermatozoa from captive Amazon squirrel monkeys (Saimiri collinsi Osgood, 1916) during the dry and rainy seasons

The squirrel monkey (Saimiri collinsi), a Neotropical primate endemic to the Amazon in Brazil, is used as a biological model for reproductive research on the genus Saimiri. Although this animal is known to exhibit reproductive seasonality, nothing is known about the differences in its seminal quality, sperm protein composition, or sperm protein profile between the breeding (dry) and non-breeding (rainy) seasons. Thus, the aims of this study were to evaluate the quality of S. collinsi semen during the dry and rainy seasons and to describe the global sperm proteomics and expression variations in the sperm proteins during the two seasons. Aside from the pH, there was no difference in the seminal quality between the dry and rainy seasons. The study approach based on bottom-up proteomics allowed the identification of 2343 proteins present in the sperm samples throughout these two seasons. Of the 79 proteins that were differentially expressed between the two seasons, 39 proteins that were related to spermatogenesis, sperm motility, capacitation, fecundation, and defense systems against oxidative stress were upregulated in the dry season. Knowledge on the sperm proteins provides crucial information for elucidating the underlying mechanisms associated with sperm functionality. Thus, our results help to advance our understanding of the reproductive physiology of S. collinsi, providing valuable information for the improvement of protocols used in assisted reproduction techniques for the conservation of endangered Saimiri species.

cell biology↗