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E u r o S c i C o n c o n f e r e n c e o n
Protein, Proteomics and
Computational Biology
Biochemistry & Molecular Biology Journal
ISSN: 2471-8084
D e c e m b e r 0 6 - 0 7 , 2 0 1 8
Am s t e r d a m , N e t h e r l a n d s
Proteomics and Computational Biology 2018
Page 14
R
eactivation of the male gametogenic expression program is tightly associated
with the most malignant and metastasis-prone tumours and the emergence of
aggressive sub clones of tumour cells, which are highly resistant to stress-induced
apoptosis. While the cancer-testis antigens (CTAs) CABYR and AKAP3/4 roles
during gamatogenesis and their importance for flagellar movement have gradually
emerged, their function in cancer cells have remained obscure. In this study, we
combine immunoprecipitation (IP), mass spectrometry (MS) and Western blot
(WB) analysis to unravel their functional roles in therapy resistant lung and ovary
adenocarcinoma cells by identifying their interaction partners. CABYR variants
were shown to oligomerize and interact with AKAP proteins to generate a HMW
signal scaffold structure, which was found to bind several glycolytic enzymes and
signal transducers. Forward and reverse IP experiments followed byWB confirmed
interactions between CABYR and LDH, ALDO, PFK, TPI-1, GAPDH, ENO-1 and
GSK3b. Transistion from normoxic to hypoxic growth conditions disrupted the
associations between glycolytic enzymes and the CABYR-AKAP signaling scaffold
in the cancer cells, leading to a 3.2-fold increase in their production and secretion
of lactic acid. Hypoxic growth conditions resulted in increased acetylation of
lysine residues in both CTAs, and triggered deacetylation of lysines in LDH and
aldolase. Treatment with resveratrol prevented hypoxia-induced dissociations,
suggesting that the regulation of oxygen-sensitive protein interactions within the
CABYR-AKAP-glycolysome complex involve changes in the acetylation of lysines
in the engaged proteins. MS analysis of IPs finally revealed interactions between
CABYR and proteins associated with the cancer cells contractile cytoskeleton.
Based on these findings, it is tempting to speculate that hypoxia-induced release
and subsequent local activation of glycolysomes from cytoskeleton-associated
CABYR-AKAP scaffold structures might be instrumental for cancer cells ability
to maintain a steady energy supply to their contractile cytoskeleton and thereby
sustain their migratory and invasive capability despite encountering severe
reductions in environmental oxygen levels.
Biography
Soren Naaby Hansen has graduated as MD from Copenhagen
University in 1991. Following Residential Training, he went on to
train as a Postdoctoral Fellow at the Department of Cell Biolo-
gy, University of Virginia (1993), where he later became Group
Leader in Proteomics. In 1999, he became Assistant Member
and Head of Biochemical Proteomics, Ludwig Institute for
Cancer Research, Royal Free and University College London
Medical School, UK. He became Lecturer in Biochemistry and
Molecular Biology, University College London, in 2000. In 2006,
he returned to Denmark where he was appointed as Senior Sci-
entist at the Department of Clinical Immunology, Aarhus Univer-
sity Hospital, Aalborg. He completed a Doctorate in Medical Sci-
ences at Aarhus University in 2012, and is currently employed
at the Department of Psychiatry, Aalborg University Hospital,
where he directs a study of the pathophysiology underlying de-
pression disorders.
sonh@rn.dkOxygen-sensitive interactions between
glycolytic enzymes and a cancer-testis antigen
established signalling scaffold are regulated
by lysine acetylation
Soren Naaby Hansen
1
, Arabinda Mandal
2
and Allan Stensballe
3
1
Aalborg University Hospital, Denmark
2
University of Virginia, USA
3
Aalborg University, Denmark
Soren Naaby Hansen et al., Biochem Mol biol J Volume:4
DOI: 10.21767/2471-8084-C5-019