KANK1 promotes breast cancer development by compromising Scribble-mediated Hippo activation.

KANK1 is expressed in epithelial cells and connects focal adhesions with the adjacent cortical microtubule stabilizing complex. Although KANK1 was shown to suppress cancer cell growth in vitro, TCGA database points to high KANK1 levels associated with poor prognosis in a wide spectrum of human malignancies. Here, we address this discrepancy and report that KANK1 promotes proliferation and survival of PyMT-transformed mammary tumor cells in vivo.

The USP12/46 deubiquitinases protect integrins from ESCRT-mediated lysosomal degradation.

The functions of integrins are tightly regulated via multiple mechanisms including trafficking and degradation. Integrins are repeatedly internalized, routed into the endosomal system and either degraded by the lysosome or recycled back to the plasma membrane. The ubiquitin system dictates whether internalized proteins are degraded or recycled.

Complete all-atom hydrodynamics of protein unfolding in uniform flow.

The unfolding dynamics of a protein, ubiquitin, pinned in several uniform flows, was studied at low and high flow rates in an all-atom style through a non-equilibrium molecular dynamics approach with explicit water molecules included. Atomic hydrodynamic force components on individual amino acids, as a function of time, due to the collisional interactions with the flowing water molecules were calculated explicitly. The protein conformational change in response to those time-varying forces was computed completely at the high flow rate up to nanosecond until the fully stretched state was reached.

Atomic hydrodynamics of DNA: coil-uncoil-coil transitions in a wall-bounded shear flow.

Extensive experimental work on the response of DNA molecules to externally applied forces and on the dynamics of DNA molecules flowing in microchannels and nanochannels has been carried out over the past two decades, however, there has not been available, until now, any atomic-scale means of analyzing nonequilibrium DNA response dynamics. There has not therefore been any way to investigate how the backbone and side-chain atoms along the length of a DNA molecule interact with the molecules and ions of the flowing solvent and with the atoms of passing boundary surfaces. We report here on the application of the nonequilibrium biomolecular dynamics simulation method that we developed [G.

Non-equilibrium all-atom molecular dynamics simulations of free and tethered DNA molecules in nanochannel shear flows.

In order to gain insight into the mechanical and dynamical behaviour of free and tethered short chains of ss/ds DNA molecules in flow, and in parallel to investigate the properties of long chain molecules in flow fields, we have developed a series of quantum and molecular methods to extend the well developed equilibrium software CHARMM to handle non-equilibrium dynamics. These methods have been applied to cases of DNA molecules in shear flows in nanochannels. Biomolecules, both free and wall-tethered, have been simulated in the all-atom style in solvent-filled nanochannels.