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Novel Physiological Targets of Fic‐mediated Adenylylation/AMPylation
Author(s) -
Mattoo Seema,
Sanyal Anwesha
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.602.8
Subject(s) - adenylylation , gtpase , microbiology and biotechnology , chemistry , political science , biology , enzyme , biochemistry , biosynthesis
Post‐translational modification (PTM) of proteins is a common theme in signal transduction. We previously discovered a family of enzymes, defined by a ‘Fic’ domain, that covalently attach an adenosine monophosphate (AMP) to their targets to alter cellular signaling. This PTM, called Fic‐mediated adenylylation/AMPylation is a strategy used by some bacterial pathogens to adenylylate and inactivate host Rho GTPases, thus evading host defense mechanisms. Recently we demonstrated that the sole human Fic, HYPE, adenylylates the ER molecular chaperone, BiP, thereby functioning as a key regulator of ER homeostasis. Accordingly, we showed that HYPE localizes to the ER lumen to modify BiP and alter the unfolded protein response (UPR) to stress. Using electron tomography and biochemical analyses, here we report that HYPE localizes to cellular compartments other than the ER, and have identified new physiologically relevant protein targets for HYPE. Validation of these targets is discussed. Support or Funding Information This work was supported by funding from 1) an Indiana CTSI (Clinical and Translational Sciences Institute) Core Pilot Grant, 2) a Showalter Research Trust Award, 3) an American Cancer Society (ACS) Institutional Grant, and 4) the National Institute Of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH) under Award Number R01GM100092.