Compositions and methods for inhibiting cancer cell metastasis and inflammation are disclosed. The methods generally involve administering to a subject a composition containing an agent that selectively inhibits the binding of p68 RNA helicase to calmodulin (CaM) in the cells.

The present invention is within the field of protein engineering and purification. The invention relates to a target-binding polypeptide mutant of an IgG binding polypeptide, such as Protein A, Protein G, Protein L or Protein M, comprising a metal binding motif. More closely the invention relates to an Fc binding ligand comprising an engineered protein based on the Protein A derived Z domain, to which a calcium binding EF-loop has been introduced.

Therapeutic proteins for inducing apoptosis in cells and method for using such proteins are described. The protein, e.g., a chimeric protein, has a host peptide fused to a more stable BH3 domain peptide. The host peptide may be Calbindin D9k, a N-terminal or C-terminal half-domain of Calmodulin, Parvalbimin (“Pa”), an amino acid sequence variant thereof, or a modified variant thereof. The BH3 domain may be Bim, Bid, Bad, Bik, Bmf, Hrk, Puma, or Noxia. Moreover, various conjugates may be attached to the chimeric protein, including a folate and polyethylene glycol.

[Problem] Provided is a calmodulin-like skin protein (CLSP) derivative, which has an activity to suppress neuronal cell dysfunction or cell death associated with e.g., Alzheitner's disease stronger than of humanin, and which is insensitive to an inhibitory action by an inhibitor of the activity; a polypeptide which has an action/activity to potentiate or protect the Alzheimer's disease-suppressing activity by CLSP; and the like.

[Solution] A derivative (mutant) of calmodulin-like skin protein (CLSP), characterized by including an endogenous humanin-homogenous region (EHR), which is the core of the activity to suppress the neuronal cell dysfunction or neuronal cell death associated with Alzheimer's disease (CLSP activity), and not including a region to which an inhibitor of the CLSP activity binds; a pharmaceutical composition to suppress the neuronal cell dysfunction or neuronal cell death associated with Alzheimer's disease, the composition including the mutant as an active ingredient; and the like.

The present invention relates to a method for diagnosing myeloid malignancy comprising determining the presence of a mutant allele of the calreticulin gene. Also genomic sequences, cDNA sequences, mRNA sequences and protein sequences of the mutant calreticulin are subject of the present invention. Further, the invention relates to medical uses of inhibitors of mutant calreticulin.

The present invention provides, for example, a set of two polypeptides exhibiting the nuclease activity with dependence on light or in the presence of a drug, in which an N-terminal side fragment and a C-terminal side fragment of a Cas9 protein are bound to each of two polypeptides which form a dimer with dependence on light or in the presence of a drug.

An in vitro electrical conductor is provided. The in vitro electrical conductor may include a plurality of Calsequestrin (CSQ) protein molecules. The CSQ protein molecules may be connected to form a tendril, a network structure, or a biological tunnel structure. An electrical device including the in vitro electrical conductor is provided. An ionic transistor including the in vitro electrical conductor is provided. An in vitro method of conducting ions from an ion source to an ion sink is further provided. The method may include providing an electrical conductor including a plurality of CSQ protein molecules and conducting ions through the electrical conductor to the ion sink. The CSQ protein molecules may be connected to form a tendril, a network structure, or a biological tunnel structure.

The present invention relates to a method for diagnosing myeloid malignancy comprising determining the presence of a mutant allele of the calreticulin gene. Also genomic sequences, cDNA sequences, mRNA sequences and protein sequences of the mutant calreticulin are subject of the present invention. Further, the invention relates to medical uses of inhibitors of mutant calreticulin.

The present invention relates to mutants of S100A12 having at least one mutation in the high-affinity calcium binding hand or the low-affinity calcium binding hand or the zinc binding region. The present invention also relates to methods of detecting S100A12 dimers in a sample as well as methods of diagnosis using the S100A12 mutant of the invention, as well as to diagnostic compositions and kits comprising such an S100A12 mutant. The present invention further relates to a method of generating an antibody that specifically binds to an S100A12 dimer using the S100A12 mutant of the invention, as well as to an antibody that specifically binds to an S100A12 dimer.

The present invention provides compositions and methods useful for treating disorders amenable to therapy via introduction of multigenic expression vectors. More particularly, the invention provides vectors and polynucleotides encoding polypeptides for treatment of cardiac disorders wherein said polypeptides may comprise a cytokine, a chemokine, and/or an angiogenic polypeptide, or functional derivatives thereof. Also provided, as compositions of the invention, are linkers useful for connecting and expressing functional (biologically active) polypeptides from single, multigenic-expression constructs.