Question 1

What is the Meaning of VCP/p97?

Accepted Answer

VCP/p97, which stands for Valosin-containing protein and is also known as p97, is a crucial adenosine triphosphatase (ATPase) belonging to the AAA+ protein family. This highly conserved protein plays a central role in various cellular processes by utilizing energy from ATP hydrolysis to remodel and unfold target proteins.

Question 2

What is the Context of VCP/p97?

Accepted Answer

Within the cellular environment, VCP/p97 operates predominantly in the cytoplasm and nucleus, acting as a molecular chaperone. It is an integral component of protein homeostasis, participating in processes such as endoplasmic reticulum-associated degradation (ERAD), autophagy, DNA damage response, and membrane fusion events. Its widespread presence underscores its fundamental importance across diverse cellular functions.

Question 3

What is the Significance of VCP/p97?

Accepted Answer

From a clinical perspective, understanding VCP/p97 is paramount due to its direct implication in human disease pathology. Mutations in the VCP gene are directly linked to inherited neurodegenerative conditions, including Inclusion Body Myopathy with Paget disease of bone and Frontotemporal Dementia (IBMPFD). Furthermore, its altered activity is observed in various cancers and viral infections, highlighting its relevance as a potential therapeutic target for patient benefit.

Question 4

What is the Mechanism of VCP/p97?

Accepted Answer

The functional activity of VCP/p97 stems from its nature as a homohexameric AAA+ ATPase. It precisely binds to ubiquitinated proteins, using the energy derived from ATP hydrolysis to unfold or extract these substrates from cellular structures. This action often prepares proteins for subsequent degradation by the proteasome or facilitates their transport and assembly, maintaining cellular integrity.

Question 5

What is the Application of VCP/p97?

Accepted Answer

Clinical research actively explores VCP/p97 as a target for novel therapeutic interventions. Specific inhibitors are under investigation for their potential in treating certain cancers by disrupting tumor cell survival pathways or in addressing neurodegenerative disorders by mitigating protein aggregation. These efforts represent a focused approach to leverage molecular insights for tangible health improvements.

Question 6

What is the Metric of VCP/p97?

Accepted Answer

While direct clinical measurement of VCP/p97 activity in routine patient care is not standard, its expression levels or functional status can be assessed in research and diagnostic settings. Techniques such as Western blotting, immunohistochemistry, and advanced biochemical assays are employed to quantify its presence or activity in patient-derived tissues or cells, providing insights into disease mechanisms and treatment responses.

Question 7

What is the Risk of VCP/p97?

Accepted Answer

Modulating VCP/p97 therapeutically presents inherent risks due to its pervasive and vital roles in cellular maintenance. Interference with its normal function could lead to unintended cellular stress, disruption of essential homeostatic pathways, or systemic toxicity. Therefore, any therapeutic intervention targeting VCP/p97 requires careful consideration of its broad physiological impact to ensure patient safety.

VCP/p97

Meaning

Context

Significance

Mechanism

Application

Metric

Risk

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