Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Selection of a dominant follicle that will ovulate likely occurs by activation of cell survival pathways and suppression of death-promoting pathways in a mechanism involving FSH and its cognate receptor (FSHR). A yeast two-hybrid screen of an ovarian cDNA library was employed to identify potential interacting partners with human FSHR intracellular loops 1 and 2. Among eight cDNA clones identified in the screen, APPL1 (adaptor protein containing PH domain, PTB domain, and leucine zipper motif; also known as APPL or DIP13alpha) was chosen for further analysis. APPL1 appears to coimmunoprecipitate with FSHR in HEK 293 cells stably expressing FSHR (293/FSHR cells), confirming APPL1 as a potential FSHR-interacting partner. The phosphorylation status of members of the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway was also examined because of the proposed role of APPL1 in the antiapoptotic PI3K/Akt pathway. FOXO1a, also referred to as forkhead homologue in rhabdomyosarcoma, is a downstream effector in the pathway and tightly linked to expression of proapoptotic genes. FOXO1a, but not the upstream kinase Akt, is rapidly phosphorylated, and FOXO1a is thereby inactivated when 293/FSHR cells are treated with FSH. In addition, FSHR coimmunoprecipitates with Akt. The identification of APPL1 as a potential interactor with FSHR and the finding that FOXO1a is phosphorylated in response to FSH provide a possible link between FSH and PI3K/Akt signaling, which may help to delineate a survival mechanism whereby FSH selects the dominant follicle to survive.
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PMID:Human follicle-stimulating hormone (FSH) receptor interacts with the adaptor protein APPL1 in HEK 293 cells: potential involvement of the PI3K pathway in FSH signaling. 1507 Aug 27

Sonic hedgehog (Shh) and its main receptor, Patched (Ptc), are implicated in both neural development and tumorigenesis. Besides its classic morphogenic activity, Shh is also a survival factor. Along this line, Ptc has been shown to function as a dependence receptor; it induces apoptosis in the absence of Shh, whereas its pro-apoptotic activity is blocked in the presence of Shh. Here we show that, in the absence of its ligand, Ptc interacts with the adaptor protein DRAL (downregulated in rhabdomyosarcoma LIM-domain protein; also known as FHL2). DRAL is required for the pro-apoptotic activity of Ptc both in immortalized cells and during neural tube development in chick embryos. We demonstrate that, in the absence of Shh, Ptc recruits a protein complex that includes DRAL, one of the caspase recruitment (CARD)-domain containing proteins TUCAN (family member, 8) or NALP1 (NLR family, pyrin domain containing 1) and apical caspase-9. Ptc triggers caspase-9 activation and enhances cell death through a caspase-9-dependent mechanism. Thus, we propose that in the absence of its ligand Shh the dependence receptor Ptc serves as the anchor for a caspase-activating complex that includes DRAL, and caspase-9.
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PMID:The Patched dependence receptor triggers apoptosis through a DRAL-caspase-9 complex. 1946 23

V-crk avian sarcoma virus CT10 oncogene homolog-like (CRKL) is a member of CRK family. It acts as an adaptor protein in intracellular signal transduction. CRKL has been reported overexpressed in a variety of cancers affecting the aggressive and malignant behaviors of cancer cells. CRKL seems to show a tumor-promotion role in gastric cancer, glioblastoma multiforme, hepatocellular carcinoma, bladder cancer, lung cancer, colon cancer, ovarian cancer, leukemia, breast cancer, head and neck cancer, rhabdomyosarcoma and neuroblastoma. The association of CRKL with malignant tumors and its potential action mechanisms were summarized. CRKL has the potential to be used as a biomarker for the diagnosis, treatment and prognosis of certain tumors.
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PMID:The role of CT10 regulation of kinase-like in cancer. 2553 Oct 52

Mitochondrial antiviral signaling protein (MAVS), a crucial adaptor protein localized on mitochondria, plays vital roles in various biological processes. Autophagy and apoptosis are two independent and closely linked cell death pathways. But whether MAVS could induce apoptosis and autophagy in rhabdomyosarcoma cells (RD cells) and what is the relationship between autophagy and apoptosis still remains elusive. Here, we reveal that overexpression of MAVS could trigger both apoptosis and autophagy in RD cells. Interestingly, MAVS-induced apoptosis was dependent on the activation of the c-Jun N-terminal kinase (JNK) signaling pathway and inhibition of the extracellular signal-regulated kinase (ERK) signaling pathway. Also, it was found that inhibition of autophagy by 3-methyladenine (3-MA) enhanced MAVS-induced apoptosis resulting in increased cleavage of caspase-3 and poly (ADP-ribose) polymerase (PARP). Meanwhile, autophagy induction by rapamycin resulted in decreased MAVS-induced apoptosis. In addition, we found that MAVS expression was inhibited upon Coxsackievirus A16 (CA16) infection and overexpression of MAVS could inhibit CA16 replication. Collectively, our study provides novel insights into the link between apoptosis and autophagy induced by MAVS overexpression in RD cells and gains a greater understanding of MAVS-induced antiviral functions, which provide new targets for CA16 treatment. Keywords: CA16; MAVS; apoptosis; autophagy.
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PMID:Autophagy triggered by MAVS inhibits Coxsackievirus A16 replication. 3180 82