Department of Biochemistry

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https://dspace.uohyd.ac.in/handle/1/108

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Browsing Department of Biochemistry by Author "Acconcia, Filippo"
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    An inherent role of integrin-linked kinase-estrogen receptor α interaction in cell migration
    ( 2006-11-15) Acconcia, Filippo ; Manavathi, Bramanandam ; Mascarenhas, Joseph ; Talukder, Amjad H. ; Mills, Gordon ; Kumar, Rakesh
    Integrin-linked kinase (ILK) and estrogen receptor (ER)-α modulate cell migration. However, the crosstalk between ERα and ILK and the role of ILK in ERα-mediated cell migration remain unexplored. Here, we report that ILK participates in ERα signaling in breast cancer cells. We found that ILK binds ERα in vitro and in vivo through a LXXLL motif in ILK. Estrogen prevented ERα-ILK binding, resulting in phosphatidylinositol 3-kinase (PI3K)-dependent increase in ILK kinase activity. Furthermore, the regulation of ERα-ILK interaction was dependent on the PI3K pathway. Unexpectedly, transient knockdown or inhibition of ILK caused hyperphosphorylation of ERα Ser118 in an extracellular signal-regulated kinase/ mitogen-activated protein kinase pathway-dependent manner and an enhanced ERa recruitment to the target chromatin and gene expression, a process reversed by overexpression of ILK. Compatible with these interactions, estrogen regulated cell migration via the PI3K/ILK/AKT pathway with stable ILK overexpression hyperactivating cell migration. Thus, status of ILK signaling may be an important modifier of ER signaling in breast cancer cells and this pathway could be exploited for therapeutic intervention in breast cancer cells. ©2006 American Association for Cancer Research.
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    An inherent role of microtubule network in the action of nuclear receptor
    ( 2006-10-24) Manavathi, Bramanandam ; Acconcia, Filippo ; Rayala, Suresh K. ; Kumar, Rakesh
    Estrogen receptor α (ERα) functions as both a transcription factor and a mediator of rapid estrogen signaling. Recent studies have shown a role for ERα-interacting membranous and cytosolic proteins in ERα action, but our understanding of the role of the microtubule network in the modulation of ERα signaling remains unclear. Here we found that endogenous ERα associates with microtubules through the microtubule-binding protein hematopoietic PBX-interaction protein (HPIP). Biochemical and RNA-interference studies demonstrated that HPIP influences ERα-dependent rapid estrogen signaling by acting as a scaffold protein and recruits Src kinase and the p85 subunit of phosphatidylinositol 3-kinase to a complex with ERα, which in turn stimulates AKT and MAPK. We also found that ERα interacts with β-tubulin through HPIP. Destabilization of microtubules activated ERα signaling, whereas stabilization of microtubules repressed ERα transcriptional activity in a HPIP-dependent manner. These findings revealed a role for HPIP-microtubule complex in regulating 17β-estradiol-ERα responses in mammalian cells and discovered an inherent role of microtubules in the action of nuclear receptor. © 2006 by The National Academy of Sciences of the USA.