Mammalian variations on a theme: a Smo and Sufu surprise.
نویسنده
چکیده
Hedgehog signaling plays a critical role during development and tumorigenesis. While much mechanistic insight has come from pathway investigations in the fruit fly, recent studies suggest a distinct mammalian strategy for signaling from Smoothened to Gli through the novel protein Suppressor of Fused that may have therapeutic implications.
منابع مشابه
Cilium-independent regulation of Gli protein function by Sufu in Hedgehog signaling is evolutionarily conserved.
A central question in Hedgehog (Hh) signaling is how evolutionarily conserved components of the pathway might use the primary cilium in mammals but not fly. We focus on Suppressor of fused (Sufu), a major Hh regulator in mammals, and reveal that Sufu controls protein levels of full-length Gli transcription factors, thus affecting the production of Gli activators and repressors essential for gra...
متن کاملA mechanism for vertebrate Hedgehog signaling: recruitment to cilia and dissociation of SuFu–Gli protein complexes
In vertebrates, Hedgehog (Hh) signaling initiated in primary cilia activates the membrane protein Smoothened (Smo) and leads to activation of Gli proteins, the transcriptional effectors of the pathway. In the absence of signaling, Gli proteins are inhibited by the cytoplasmic protein Suppressor of Fused (SuFu). It is unclear how Hh activates Gli and whether it directly regulates SuFu. We find t...
متن کاملDual phosphorylation of Suppressor of fused by PKA and GSK3β regulates its stability and localization in the primary cilium
Suppressor of fused (Sufu) is an essential negative regulator of the Sonic hedgehog (Shh) pathway, but little is known about how Sufu itself is normally regulated. Here, we report that Sufu is phosphorylated at S342 and S346 by GSK3β and cAMP-dependent protein kinase A (PKA), respectively, and phosphorylation at this dual site stabilizes Sufu against Shh signaling-induced degradation. We furthe...
متن کاملMerkel Cell Carcinoma with a Suppressor of Fused (SUFU) Mutation: Case Report and Potential Therapeutic Implications
INTRODUCTION Merkel cell carcinoma is a neuroendocrine malignancy. Suppressor of fused (SUFU) is a tumor suppressor oncogene that participates in the Hedgehog (Hh) signaling pathway. The aim of the study was to describe a patient whose Merkel cell carcinoma demonstrated a SUFU genomic alteration. CASE STUDY The Hh signaling pathway is involved in the pathogenesis of several tumors, including ...
متن کاملMutational Analysis of Hedgehog Signaling Pathway Genes in Human Malignant Mesothelioma
BACKGROUND The Hedgehog (HH) signaling pathway is critical for embryonic development and adult homeostasis. Recent studies have identified regulatory roles for this pathway in certain cancers with mutations in the HH pathway genes. The extent to which mutations of the HH pathway genes are involved in the pathogenesis of malignant mesothelioma (MMe) is unknown. METHODOLOGY/PRINCIPAL FINDINGS R...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Developmental cell
دوره 10 2 شماره
صفحات -
تاریخ انتشار 2006