Congratulations!!

💊 Learn more at subunit.org :)

Vismodegib turning off the signals transmitted by SMO

Vismodegib is a medication that binds to SMO and inactivates it. This turns off the constant signals transmitted by SMO, halting cancer growth.

[10/10]

In either case, these mutations allow SMO-mediated signals to be transmitted uncontrollably even in the absence of HH. These types of cancer rely on signals from the constitutively active hedgehog pathway to grow.

[9/10]

Mutated SMO entering the primary cilium in the absence of HH

However, in certain types of cancer, such as basal cell carcinoma, mutations in SMO allows it to bypass PTCH and enter the primary cilium. Alternatively, mutations in PTCH prevents it from blocking the entry of SMO into the primary cilium.

[8/10]

Since this process is dependent on the presence of HH, it is a controllable one — when cellular growth and differentiation is no longer needed, the production of HH simply ceases.

[7/10]

HH-bound PTCH is transported into the cell; without PTCH as a gatekeeper, SMO enters the primary cilium, leading to signal transmission

On the other hand, when HH binds to PTCH, PTCH is inactivated and is transported into the cell. This allows SMO to enter the primary cilium, where it is able to transmit signals for the cell to grow and differentiate.

[6/10]

In general, PTCH resides on the surface of the cell near the primary cilium, while SMO resides within the cell. Through mechanisms that are not yet fully understood, PTCH acts as a gatekeeper that prevents SMO from entering the primary cilium.

[5/10]

PTCH on the surface of the cell and the primary cilium, along with SMO within the cell

Three key proteins are involved in the hedgehog pathway: smoothened (SMO), patched (PTCH), and hedgehog (HH).

[4/10]

Most notably, it plays a key role in cellular growth and differentiation through the hedgehog pathway, and the dysfunction in this pathway is implicated in many diseases, including cancer.

[3/10]

Primary cilium receiving and transmitting signals

A primary cilium is a single antenna-like structure that protrudes out of most cells in our body. It functions as a signaling hub that receives and transmits a variety of signals inside and outside the cell.

[2/10]

Vismodegib in its active biological context

Vismodegib (marketed as Erivedge) is a medication used to treat adults with metastatic or locally advanced basal cell carcinoma.

How does it work?

[1/10]

💊 Learn more at subunit.org

Belzutifan disrupting the interaction between HIF-2α and HIF-1β

Belzutifan is a drug that disrupts the interaction between HIF-2α and HIF-1β. This turns off the constant expression of survival genes, halting cancer growth.

[9/9]

Active HIF complex activating survival genes under normal oxygen levels

As a result, HIF-2α accumulates and constantly activates survival genes, leading to uncontrolled cellular growth, i.e., cancer.

[8/9]

Without functional VHL proteins, HIF-2α with hydroxylated prolines is not degraded

However, patients with von Hippel-Lindau disease possess mutations in the gene encoding VHL protein that prevent functional VHL proteins from being produced. Therefore, HIF-2α is not degraded under normal oxygen levels, even when its prolines are hydroxylated.

[7/9]

VHL recognizing hydroxylated prolines in HIF-2α, leading to HIF-2α degradation

Hydroxylated prolines are recognized by a protein called VHL, which then marks HIF-2α for degradation. This ensures that the HIF complex-associated genes are not active when oxygen levels are normal.

[6/9]

PHD using oxygen molecules to hydroxylate prolines on HIF-2α

On the other hand, under normal oxygen levels, a protein called PHD uses the amply available oxygen molecules to modify the prolines in HIF-2α. This modification results in hydroxylated prolines.

[5/9]

Active HIF complex binding to DNA and activating survival genes

This complex then seeks out specific segments of DNA, where it activates genes involved in cellular adaptation to low oxygen levels and survival.

[4/9]

HIF-2α and HIF-1β combining to form active HIF complex

When oxygen levels are low, HIF-2α binds to another protein called HIF-1β to form an active HIF complex.

[3/9]

HIF-2α with two prolines highlighted

HIF-2α is a protein that orchestrates cellular response and adaptation to low oxygen levels. Notably, it contains proline motifs that are crucial for regulating its activity.

[2/9]

Belzutifan in its active biological context

Belzutifan (marketed as Welireg) is a medication used to treat cancers associated with von-Hippel Lindau (VHL) disease.

How does it work?

[1/9]

Although they are very effective, these drugs are all known to have pretty tough side effect profiles. I hope the treatment is successful for you!

I’m glad this was helpful. I hope you have a successful treatment!

Therefore, lenalidomide, by leading to Ikaros degradation, halts their growth and ultimately leads to cancer cell death.

[5-b/5]

Lenalidomide treatment leads to Ikaros degradation, ultimately resulting in cancer cell death

Ikaros is a protein essential for the development of B cells, a type of immune cell. Some cancers that originate from B cells, such as multiple myeloma, rely on Ikaros to drive their uncontrolled growth.

[5-a/5]

Cereblon, with lenalidomide bound, recruiting Ikaros

Lenalidomide is a drug that binds to cereblon at its target protein-binding site. This alters the target protein specificity of cereblon towards another family of proteins called Ikaros. As a result, Ikaros proteins are marked with ubiquitin and degraded.

[4/5]

Other proteins, such as cereblon, recruit specific target proteins, ensuring that only proteins that need to be degraded are marked with ubiquitin.

[3-b/5]

Ubiquitin ligase attaching ubiquitin to a target protein recruited by cereblon

Ubiquitination is one of the pathways cells utilize to degrade proteins. In this pathway, a protein called ubiquitin ligase tags a target protein with ubiquitin, which serves as a signal for protein degradation.

[3-a/5]

Protein degradation and recycling

Protein degradation is an important process that enables cells to eliminate abnormal or unnecessary proteins, recycle protein components, and adapt to changing cellular conditions.

[2/5]