GAGE cancer-germline antigens bind DNA and are recruited to the nuclear envelope by Germ cell-less

Bidragets oversatte titel: GAGE proteiner binder DNA og rekrutteres til kernemembranen af GCL

Morten Gjerstorff, Heike Rösner, Christina Bøg Pedersen, Katrine Buch Vidén Greve, Steffen Schmidt, Katherine Wilson, Jan Mollenhauer, Hüseyin Besir, Flemming Poulsen, Niels Erik Møllegaard, Henrik Ditzel

Publikation: Konferencebidrag uden forlag/tidsskriftPosterForskning

Abstrakt

GAGE genes encode a highly similar, primate-specific protein family with unique primary structure and undefined roles in germ cells, various fetal cells and cancer cells. We report that GAGE proteins are intrinsically disordered proteins that provide novel interfaces between chromatin and the nuclear envelope. Structural analysis by NMR and CD spectroscopy showed GAGE proteins lack distinct secondary or tertiary structure and are therefore intrinsically disordered. In normal cells and cancer cells GAGE proteins localize predominantly in the nucleus; we found GAGE proteins formed stable complexes with dsDNA at sub-physiological concentrations. GAGE12I bound several different dsDNA fragments, suggesting sequence-independent binding. GAGE1, GAGE2B and GAGE12I associated directly or indirectly with Germ cell-less (GCL), which directly binds LEM-domain proteins (LAP2β, emerin, MAN1) at the nuclear envelope. Furthermore, exogenous and endogenous GAGE proteins were recruited to the nuclear envelope in GCL-overexpressing cells. Gene expression analysis and immunohistochemical staining suggest GAGE proteins and GCL interact physiologically in human cells that express both, including male germ cells and most types of cancer. The dual interaction of GAGE with dsDNA and GCL propose a novel mechanism of chromatin regulation in germ cells and tumorigenesis.
Bidragets oversatte titelGAGE proteiner binder DNA og rekrutteres til kernemembranen af GCL
OriginalsprogEngelsk
Publikationsdato5. dec. 2011
StatusUdgivet - 5. dec. 2011
BegivenhedChromatin structure & function -
Varighed: 5. dec. 2011 → …

Konference

KonferenceChromatin structure & function
Periode05/12/2011 → …

Emneord

  • cancer

Citationsformater