The Hedgehog pathway is one of the most commonly affected signaling pathways in Basal Cell Carcinoma. The diagram of the pathway is as follows:
Hedgehog (SHH) —–>| Patched (PTCH) —-| Smoothened (SMO) —-> GLI.
In the above pathway, a mutation can occur in the PTCH protein that results in increased signaling, which can lead to cancer. In this case, PTCH is a:
A. Intramembrane Protein
B. Promiscuous Kinase
C. Proto-Oncogene
D. Tumor Suppressor
E. Tyrosine Kinase
Correct answer: D
In this case Patched (PTCH) normally suppresses SMO, thus preventing increased signaling and gene transcription. In this sense it is acting as a tumor suppressor. Protein patched homolog 1 is a protein that is the member of the Patched family and in humans is encoded by the PTCH1 gene.
(A) PRCH1 is not a intramembrane protein, it is a transmembrane protein.
(B) PTCH1 functions as a tumor suppressor, but not a promiscuous Kinase
(C) PTCH1 functions as a tumor suppressor, but not a Proto-Oncogene,
(E) PTCH1 functions as a tumor suppressor, but not a Tyrosine Kinase
Educational objectives
PTCH1 is a member of the patched gene family and is the receptor for sonic hedgehog, a secreted molecule implicated in the formation of embryonic structures and in tumorigenesis. This gene functions as a tumor suppressor. The PTCH1 gene product, is a transmembrane protein that suppresses the release of another protein called smoothened, and when sonic hedgheog binds PTCH1, smoothened is released and signals cell proliferation.
References:
Johnson RL, Rothman AL, Xie J, Goodrich LV, Bare JW, Bonifas JM, Quinn AG, Myers RM, Cox DR, Epstein EH Jr, Scott MP (Aug 1996). “Human homolog of patched, a candidate gene for the basal cell nevus syndrome”. Science 272 (5268): 1668–71.
