Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.1 (hexokinase)
 5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The maturation of spermatozoa throughout the epididymal environment occurs in the complete absence of nuclear protein biosynthesis. As such, these cells rely heavily on posttranslational modifications of existing proteins in order to obtain the potential for fertilization. We have used an OxiCat approach to label both free and oxidized cysteine residues in rat sperm proteins and compared the ratio of reduced:oxidized peptides as these cells undergo epididymal transit. In all, 20 peptides, corresponding to 15 proteins, underwent a change in their redox status. Included in this list were A-kinase anchoring protein 4 and fatty acid-binding protein 9. Both of these proteins undergo intradisulfide bonding, leading to reduced solubility and, in the case of the latter, is likely to cause a loss of protein function. Interestingly, two glycolytic enzymes, hexokinase-1 and lactate dehydrogenase, also display increased cysteine oxidation during epididymal transit, which may be involved in the regulation of the enzyme activities.
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PMID:Analysis of protein thiol changes occurring during rat sperm epididymal maturation. 2541 90

Poly(ADP-ribose) polymerase (PARP1) is a nuclear protein that is activated by binding to DNA lesions and catalyzes poly(ADP- ribosyl)ation of nuclear acceptor proteins, including PARP1 itself, to recruit DNA repair machinery to DNA lesions. When excessive DNA damage occurs, poly(ADP-ribose) (PAR) produced by PARP1 is translocated to the cytoplasm, changing the activity and localization of cytoplasmic proteins e.g. apoptosis-inducing factor (AIF), hexokinase and resulting in cell death. This cascade, termed parthanatos, is a caspase-independent programmed cell death distinct from necrosis and apoptosis. In contrast, PARP1 is a substrate of activated caspases 3 and 7 in caspase-dependent apoptosis. Once cleaved, PARP1 loses its activity, thereby suppressing DNA repair. Caspase cleavage of PARP1 occurs within a nuclear localization signal near the DNA-binding domain, resulting in the formation of 24-kDa and 89-kDa fragments. In the current study, we found that caspase activation by staurosporine- and actinomycin D-induced PARP1 auto-poly(ADP-ribosyl)ation and fragmentation, generating poly(ADP-ribosyl)ated 89-kDa and 24-kDa PARP1 fragments. The 89-kDa PARP1 fragments with covalently attached PAR polymers were translocated to the cytoplasm, while 24-kDa fragments remained associated with DNA lesions. In the cytoplasm, AIF binding to PAR attached to the 89-kDa PARP1 fragment facilitated its translocation to the nucleus. Thus, the 89-kDa PARP1 fragment is a PAR carrier to the cytoplasm, inducing AIF release from mitochondria. Elucidation of the caspase-mediated interaction between apoptosis and parthanatos pathways extend the current knowledge on mechanisms underlying programmed cell death and may lead to new therapeutic targets.
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PMID:The 89-kDa PARP1 cleavage fragment serves as a cytoplasmic PAR carrier to induce AIF-mediated apoptosis. 3316 26