Targeting the Nuclear Import Receptor Kpnβ1 as an Anticancer Therapeutic.

Karyopherin beta 1 (Kpnβ1) is a nuclear transport receptor that imports cargoes into the nucleus. Recently, elevated Kpnβ1 expression was found in certain cancers and Kpnβ1 silencing with siRNA was shown to induce cancer cell death. This study aimed to identify novel small molecule inhibitors of Kpnβ1, and determine their anticancer activity.

Inhibition of the nuclear transporter, Kpnβ1, results in prolonged mitotic arrest and activation of the intrinsic apoptotic pathway in cervical cancer cells.

The karyopherin β proteins are involved in nuclear-cytoplasmic trafficking and are crucial for protein and RNA subcellular localization. We previously showed that Kpnβ1, a nuclear importin protein, is overexpressed in cervical cancer and is critical for cervical cancer cell survival and proliferation, whereas non-cancer cells are less dependent on its expression. This study aimed to identify the mechanisms by which inhibition of Kpnβ1 results in cervical cancer cell death.

The expanding family of FERM proteins.

Our understanding of the FERM (4.1/ezrin/radixin/moesin) protein family has been rapidly expanding in the last few years, with the result that many new physiological functions have been ascribed to these biochemically unique proteins. In the present review, we will discuss a number of new FRMD (FERM domain)-containing proteins that were initially discovered from genome sequencing but are now being established through biochemical and genetic studies to be involved both in normal cellular processes, but are also associated with a variety of human diseases.

Willin, an upstream component of the hippo signaling pathway, orchestrates mammalian peripheral nerve fibroblasts.

Willin/FRMD6 was first identified in the rat sciatic nerve, which is composed of neurons, Schwann cells, and fibroblasts. Willin is an upstream component of the Hippo signaling pathway, which results in the inactivation of the transcriptional co-activator YAP through Ser127 phosphorylation. This in turn suppresses the expression of genes involved in cell growth, proliferation and cancer development ensuring the control of organ size, cell contact inhibition and apoptosis.