Nuclear proteasomes buffer cytoplasmic proteins during autophagy compromise.

Autophagy is a conserved pathway where cytoplasmic contents are engulfed by autophagosomes, which then fuse with lysosomes enabling their degradation. Mutations in core autophagy genes cause neurological conditions, and autophagy defects are seen in neurodegenerative diseases such as Parkinson's disease and Huntington's disease. Thus, we have sought to understand the cellular pathway perturbations that autophagy-perturbed cells are vulnerable to by seeking negative genetic interactions such as synthetic lethality in autophagy-null human cells using available data from yeast screens.

p37 regulates VCP/p97 shuttling and functions in the nucleus and cytosol.

The AAA-ATPase valosin-containing protein (VCP; also called p97 or Cdc48), a major protein unfolding machinery with a variety of essential functions, localizes to different subcellular compartments where it has different functions. However, the processes regulating the distribution of VCP between the cytosol and nucleus are not understood. Here, we identified p37 (also called UBXN2B) as a major factor regulating VCP nucleocytoplasmic shuttling.

The Influence of Body Mass Index on Growth Factor Composition in the Platelet-Rich Plasma in Patients with Knee Osteoarthritis.

Background: An abnormally high body mass index is strongly associated with knee osteoarthritis. Usually, obese patients are excluded from clinical trials involving PRP intra-articular injections. Growth factors have been demonstrated to have a disease-modifying effect on KOA treatment, even though data on their influence on treatment effectiveness in obese patients are lacking.

SMER28 binding to VCP/p97 enhances both autophagic and proteasomal neurotoxic protein clearance.

The ability to maintain a functional proteome by clearing damaged or misfolded proteins is critical for cell survival, and aggregate-prone proteins accumulate in many neurodegenerative diseases, such as Huntington, Alzheimer, and Parkinson diseases. The removal of such proteins is mainly mediated by the ubiquitin-proteasome system and autophagy, and the activity of these systems declines in disease or with age. We recently found that targeting VCP/p97 with compounds like SMER28 enhances macroautophagy/autophagy flux mediated by the increased activity of the PtdIns3K complex I.