Identification Of New Partners Research Articles

The Tousled-like kinases regulate genome and epigenome stability: implications in development and disease.

The Tousled-like kinases (TLKs) are an evolutionarily conserved family of serine-threonine kinases that have been implicated in DNA replication, DNA repair, transcription, chromatin structure, viral latency, cell cycle checkpoint control and chromosomal stability in various organisms. The functions of the TLKs appear to depend largely on their ability to regulate the H3/H4 histone chaperone ASF1, although numerous TLK substrates have been proposed. Over the last few years, a clearer picture of TLK function has emerged through the identification of new partners, the definition of specific roles in development and the elucidation of their structural and biochemical properties. In addition, the TLKs have been clearly linked to human disease; both TLK1 and TLK2 are frequently amplified in human cancers and TLK2 mutations have been identified in patients with neurodevelopmental disorders characterized by intellectual disability (ID), autism spectrum disorder (ASD) and microcephaly. A better understanding of the substrates, regulation and diverse roles of the TLKs is needed to understand their functions in neurodevelopment and determine if they are viable targets for cancer therapy. In this review, we will summarize current knowledge of TLK biology and its potential implications in development and disease.

ChemInform Abstract: A Copper Story: From Protein Folding and Metal Transport to Cancer

AbstractReview: [73 refs.

A Copper Story: From Protein Folding and Metal Transport to Cancer

AbstractEnzymes need to fold into unique three‐dimensional structures in order to function. Copper ions are cofactors in many essential enzymes. Such enzymes need to couple polypeptide folding with metal incorporation, as the metal sites are often integrated within the folded structure. Since free copper ions are toxic, most organisms have highly specialized copper transport systems. The human cytoplasmic copper chaperone Atox1 delivers copper to P1B‐type ATPases in the Golgi, for incorporation into copper‐dependent enzymes following the secretory path. Copper plays key roles in cancer development, as copper‐dependent enzymes are needed for tumor growth and metastasis. In addition, platinum‐based drugs are exported out of cells by the copper transport machinery. Recent findings also imply that some copper transport proteins regulate cell growth and development. In this brief journey of my later career, I will discuss the roles of copper in protein folding, mechanisms of copper ion transport, and cisplatin hitchhiking. The identification of new partners for Atox1 underscore the importance of further research in this area for combating cancer.

Allocating Effort and Talent in Professional Labor Markets

In many professional service firms, new associates work long hours while competing in up-or-out promotion contests. Our model explains why. We argue that the productivity of skilled partners in professional service firms (e.g., law, consulting, investment banking, and public accounting) is quite large relative to the productivity of their peers who are competent and experienced but not well suited to the partner role. Therefore, these firms adopt personnel policies that facilitate the identification of new partners. In our model, both heavy workloads and up-or-out rules serve this purpose.

Construction of Pseudomonas aeruginosa two-hybrid libraries for high-throughput assays.

In Pseudomonas aeruginosa, identification of new partners of a protein of interest could give precious clues to decipher a biological process in which this protein is involved. However, genes encoding for partners of a protein of interest are unknown and frequently scattered throughout the genome. We describe herein the construction and the use of pan-genomic bacterial two-hybrid libraries to identify new partners of a protein of interest encoded by P. aeruginosa.

HIPK2: a multitalented partner for transcription factors in DNA damage response and developmentThis paper is one of a selection of papers published in this Special Issue, entitled 28th International West Coast Chromatin and Chromosome Conference, and has undergone the Journal's usual peer review process.

Protein phosphorylation is a widely diffuse and versatile post-translational modification that controls many cellular processes, from signal transduction to gene transcription. The homeodomain-interacting protein kinases (HIPKs) belong to a new family of serine-threonine kinases first identified as corepressors for homeodomain transcription factors. Different screenings for the identification of new partners of transcription factors have indicated that HIPK2, the best characterized member of the HIPK family, is a multitalented coregulator of an increasing number of transcription factors and cofactors. The aim of this review is to describe the different mechanisms through which HIPK2 regulates gene transcription.

Identification of new partners of the epithelial sodium channel alpha subunit

A fine regulation of the amiloride-sensitive Epithelial Sodium Channel (ENaC), made of α,β and γ subunits, is crucial for maintenance of Na + balance and blood pressure. Both β- and γ-ENaC participate in negative regulation by interacting with Nedd4-2, an E3 ubiquitin-ligase. Disruption of this interaction results in increased ENaC activity (Liddle syndrome). By two-hybrid screenings, we identified new potential partners of α-ENaC: WWP1 (E3 ubiquitin-ligase protein), UBC9 and TSG101 (E2 ubiquitin/SUMO-conjugating enzymes) and confirmed these interactions in GST pull-down assays. All these partners are implicated in protein trafficking and could be involved in the regulation of ENaC activity. To cite this article: L. Malbert-Colas et al., C. R. Biologies 326 (2003).

SH3GLB, a New Endophilin-Related Protein Family Featuring an SH3 Domain

A new cDNA encoding a protein of 362 amino acids designated SH3GLB1, for SH3 domain GRB2-like endophilin B1, was identified in a yeast two-hybrid screen devoted to the identification of new partners interacting with the apoptosis inducer Bax. SH3GLB1 shows strong similarities to the SH3 domain-containing proteins of the endophilin family and presumably represents the human homologue of the potential Caenorhabditis elegans SH3 containing-protein identified by systematic translation of the C. elegans genome (GenBank Accession No. U46675). Reversing prey to bait in the yeast screen, a second protein, SH3GLB2, of 395 amino acids showing65% identity to SH3GLB1 was identified as an interactingpartner of SH3GLB1. The discovery of SH3GLB1 itself in the screening with SH3GLB1 as a bait and further mapping experiments demonstrated that a core coiled-coil-type region isrequired for the formation of SH3GLB homo- and/orheterodimers, whereas the SH3 domain is not involved in these interactions. Interestingly, the similarities with the endophilin proteins cover the entire sequence of the SH3GLB family, suggesting a common fold and presumably a common mode of action. Furthermore, SH3GLB members colocalize to the cytoplasmic compartment of the cell together with Bax and are excluded from the nucleus.SH3GLB1 and SH3GLB2 do not significantly influence the onset and time course of Bax-mediated apoptosis in HeLa or 293T cells.

Ten novel 11q23 chromosomal partner sites. European 11q23 Workshop participants.

The MLL gene located at 11q23 has been described as a 'promiscuous' gene due its involvement with a large number of genetic partners. The EU Concerted Action Workshop on 11q23 provided 550 cases for study of which 82 showed abnormalities which did not involve the established translocations or deletion of 11q23. In these 'other' cases, which included inversions and duplications, 11q23 was found to be involved with 25 chromosome partners of which 10 had not been previously reported. These were 1q31, 4p11, 6q13, 8q21, 10q22, 10q25, 11q11, 11q21, 13q34 and 18q23. This study demonstrated the value of the Workshop, in confirming the diversity of chromosomal partner sites involved with 11q23 and in the identification of new partners.