Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Affinity purified antibodies to type I and type II regulatory subunits (RI and RII, respectively) of cAMP-dependent protein kinase were utilized to identify and localize the cAMP receptor proteins in growing vs regressing MCF-7 tumors in nude mice. In the nuclear extracts of growing tumors the RI antibody immunoprecipitated cAMP receptor protein of 47,000 daltons, whereas the RII antibody precipitated 44,000- and 34,000-dalton cAMP receptor proteins. Following estrogen withdrawal, new species of cAMP receptor proteins with molecular weights of 50,000 and 52,000 appeared in the nuclei of regressing tumors. The 50,000- and 52,000-dalton proteins were specifically precipitated by the RII antibody but not by RI antibody. Indirect immunofluorescence revealed that during regression of MCF-7 tumors, the intensity of immunofluorescence of RII antibody crossreacting cAMP binding proteins dramatically increased in the nucleoli whereas the immunofluorescence of RI remained the same. These results suggest a regulatory role of RII in mammary cancer regression.
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PMID:Appearance of 50,000- and 52,000-dalton cAMP receptor proteins in the nucleoli of regressing MCF-7 human breast cancer upon estrogen withdrawal. 636 Mar 84

Autophagy is a catabolic process in which cell components are degraded to maintain cellular homeostasis by nutrient limitations. Defects of autophagy are involved in numerous diseases, including cancer. Here, we demonstrate a new role of phospholipase D (PLD) as a regulator of autophagy. PLD inhibition enhances autophagic flux via ATG1 (ULK1), ATG5 and ATG7, which are essential autophagy gene products critical for autophagosome formation. Moreover, PLD suppresses autophagy by differentially modulating phosphorylation of ULK1 mediated by mTOR and adenosine monophosphate-activated protein kinase (AMPK), and by suppressing the interaction of Beclin 1 with vacuolar-sorting protein 34 (Vps34), indicating that PLD coordinates major players of the autophagic pathway, AMPK-mTOR-ULK1 and Vps34/Beclin 1. Ultimately, PLD inhibition significantly sensitized in vitro and in vivo cancer regression via genetic and pharmacological inhibition of autophagy, providing rationale for a new therapeutic approach to enhancing the anticancer efficacy of PLD inhibition. Collectively, we show a novel role for PLD in the molecular machinery regulating autophagy.
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PMID:Phospholipase D-mediated autophagic regulation is a potential target for cancer therapy. 2431 1