Molecular Mechanism of VCP/p97 in Health and Diseases

Dear Colleagues,

VCP, also known as p97 or TERA in humans, or cdc48 in yeast, is emerging as a master regulator of nearly all cellular functions, including organelle/protein degradation, gene transcription, cell cycle progression and membrane fusion/trafficking. It is one of the one of the most abundant proteins is one of the most abundant proteins in Eukaryotic cells comprising of ∼1% of proteins in the cell cytosol. The function of VCP in multiple cellular processes is linked to its ability to unfold proteins and target them for protein degradation. To accurately select the appropriate proteins to unfold in a timely fashion, VCP is assisted by a set of 40+ proteins called cofactors. Presumably these cofactors are implicated in the accurate and timely selection and recruitment of various substrates to VCP, with some cofactors being involved in the unfolding reaction itself. More than one 100 mutations in the VCP gene have been reported to cause severe diseases in humans, with patients developing a diverse range of pathologies including inclusion body myopathy, Paget disease of bone, frontotemporal dementia, and other neurological disorders. VCP has also been shown to be essential for the replication of some viruses and has been identified as a target for cancer treatment. The scope of this Special Issue is to highlight current knowledge and gather novel discoveries in the molecular mechanisms regulating the activity of VCP within the cell and in different tissues and their association with the development of different pathologies.

Dr. Isabelle Rouiller
Guest Editor

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• AAA ATPase
• VCP/p97/cdc48/TER ATPase
• AAA ATPase
• protein unfolding
• protein degradation
• protein quality control
• ERAD
• mitochondria-associated degradation
• lysosome degradation
• ribosome-associated degradation
• membrane fusion and trafficking
• ubiquitin
• TDP43
• inclusion body myopathy (IBM)
• paget disease (PD)
• frontotemporal dementia (FD)
• MSP1
• amyotrophic lateral sclerosis (ALS)
• charcot-marie-tooth disease 2Y
• Parkinson’s disease
• intellectual development disabilities (IDDs)
• lysosomal diseases
• tauopathies