RESEARCH: CANCER
FOLDING PROJECT #15209 PROFILE

This project looks at how a protein called PTCH1 moves cholesterol around in cells. This protein normally stops another protein, SMO, from working when it doesn't get the signal SHH. If PTCH1 doesn't work right, it can lead to cancers like medulloblastoma and basal cell carcinoma. Understanding how PTCH1 works could help us find new cancer treatments.

This project aims to elucidate the cholesterol transport mechanism in PTCH1, a transmembrane protein responsible for inhibiting SMO in the absence of SHH in the hedgehog signaling pathway by reducing access to ciliary membrane cholesterol.

Dysregulation of this pathway (such as the inability of PTCH1 to transport cholesterol and thereby inhibit SMO) has been linked to various cancers, including medulloblastoma and basal cell carcinoma.

Thus, understanding the mechanisms behind PTCH1 cholesterol transport will allow for therapeutic treatments to target these cancers.

PTCH1

Patched 1, a protein involved in the hedgehog signaling pathway.

PTCH1 is a protein that plays a crucial role in regulating cell growth and development. It acts as a receptor for the Hedgehog (SHH) signaling molecule. When SHH binds to PTCH1, it inhibits another protein called SMO, preventing the activation of downstream signaling pathways. Disruptions in PTCH1 function can lead to uncontrolled cell growth, contributing to various cancers.

SMO

Smoothened

SMO is a protein that acts as a key component in the Hedgehog (SHH) signaling pathway. When SHH binds to its receptor PTCH1, it inhibits SMO, preventing further signal transmission. However, when PTCH1 is not bound to SHH, SMO becomes activated, leading to downstream signaling events that promote cell growth and development.

SHH

Sonic Hedgehog

SHH is a signaling molecule that plays a crucial role in embryonic development and tissue homeostasis. It binds to its receptor PTCH1, initiating a signaling cascade that regulates cell growth, differentiation, and survival. Disruptions in SHH signaling can lead to developmental defects and various diseases.

Cholesterol

A type of fat molecule found in the body.

Cholesterol is a vital component of cell membranes, providing structural integrity and fluidity. It also serves as a precursor for the synthesis of various hormones, such as testosterone and estrogen. While essential for bodily functions, high levels of cholesterol can contribute to cardiovascular diseases.

Transmembrane Protein

A protein that spans the cell membrane.

Transmembrane proteins are embedded within cell membranes, extending through both the inner and outer layers. They play diverse roles in cellular processes, including transporting molecules across membranes, receiving signals from the environment, and anchoring cells to their surroundings.

Ciliary Membrane

The membrane surrounding the cilia.

Cilia are hair-like projections extending from the surface of certain cells. The ciliary membrane is a specialized structure that surrounds the cilia, regulating their function and interacting with the extracellular environment.