Direct inhibition of NF-κB activation by peptide targeting the NOA ubiquitin binding domain of NEMO.

Aberrant and constitutive NF-κB activation are frequently reported in numerous tumor types, making its inhibition an attractive target for the treatment of certain cancers. NEMO (NF-κB essential modulator) is the crucial component of the canonical NF-κB pathway that mediates IκB kinase (IKK) complex activation. IKK activation resides in the ability of the C-terminal domain of NEMO to properly dimerize and interact with linear and K63-linked polyubiquitin chains.

Characterization of reemerging chikungunya virus.

An unprecedented epidemic of chikungunya virus (CHIKV) infection recently started in countries of the Indian Ocean area, causing an acute and painful syndrome with strong fever, asthenia, skin rash, polyarthritis, and lethal cases of encephalitis. The basis for chikungunya disease and the tropism of CHIKV remain unknown. Here, we describe the replication characteristics of recent clinical CHIKV strains.

APC inactivation associates with abnormal mitosis completion and concomitant BUB1B/MAD2L1 up-regulation.

Background & Aims: Chromosomal instability, a hallmark of most colorectal cancers, has been related to altered chromosome segregation and the consequent deficit in genetic integrity. A role for the tumor suppressor gene APC has been proposed in colorectal cancer that leads to compromised chromosome segregation even though the molecular mechanism is not yet understood. Here, we tackled the genetic basis for the contribution of APC to chromosomal instability in familial adenomatous polyposis and sporadic colorectal cancer.

Heterogeneous metastasis efficiency of isogenic orthotopic colon cancer xenografts reveals distinctive gene expression profiles.

Hepatic and lung metastases are the leading causes of mortality and major indicators of aggressiveness in colorectal cancer. The underlying molecular mechanisms contributing to the development of metastasis are still unclear. Here, we designed a novel approach to explore gene expression profiles associated with metastasis in human colorectal cancer (hCRC).

Nod1-mediated innate immune recognition of peptidoglycan contributes to the onset of adaptive immunity.

Recent evidence has suggested that signals other than those from Toll-like receptors (TLRs) could contribute to the elicitation of antigen-specific immunity. Therefore, we examined the role of the Nod-like receptor (NLR) family member, Nod1, in the generation of adaptive immune responses. Our findings show that innate immune sensing of peptidoglycan by Nod1 is key for priming antigen-specific T cell immunity and subsequent antibody responses in vivo.

APC and oncogenic KRAS are synergistic in enhancing Wnt signaling in intestinal tumor formation and progression.

Background & Aims: Synchronous activation of the Wnt signaling pathway, mostly because of loss of function of the APC tumor suppressor, and of the oncogenic KRAS-signaling pathway is very frequent in colorectal cancer and is associated with poor prognosis.

Methods: We have generated a compound transgenic mouse model, KRAS(V12G)/Apc(+/1638N), to recapitulate the human disease and compared it with single transgenic littermates.

Results: Compound mutant mice are characterized by a 10-fold increase in tumor multiplicity and by accelerated tumor progression, resulting in strongly enhanced morbidity and mortality.

VirR, a response regulator critical for Listeria monocytogenes virulence.

Signature-tagged mutagenesis (STM) was used to identify new genes involved in the virulence of the Gram-positive intracellular pathogen Listeria monocytogenes. One of the mutants isolated by this technique had the transposon inserted in virR, a gene encoding a putative response regulator of a two-component system. Deletion of virR severely decreased virulence in mice as well as invasion in cell-culture experiments.

Enhanced sensitivity to irinotecan by Cdk1 inhibition in the p53-deficient HT29 human colon cancer cell line.

Mutations in the tumor-suppressor gene p53 have been associated with advanced colorectal cancer (CRC). Irinotecan (CPT-11), a DNA topoisomerase 1 inhibitor, has been recently incorporated to the adjuvant therapy. Since the DNA-damage checkpoint depends on p53 activation, the status of p53 might critically influence the response to CPT-11.