The Norwegian Cancer Society's "Research project of the month" for September went to a collaborative project between Stig Ove Bøe from the Department of Microbiology and Anne Simonsen and Pauline Isaksen from Institute of Basic Medical Sciences at UiO. Their project deals with how cells can "eat" an oncoprotein through the mechanism of autophagy.
Outcome of this project is published in the prestigious journal Blood (journal impact factor 10.56), in an article entitled "Autophagy contributes to therapy-induced degradation of the PML/RARA oncoprotein", as well as in the journal "Autophagy" (impact factor 6.83), under the heading "Autophagic degradation of an oncoprotein".
In the Blood article Bøe shares the last authorship with Simonsen, formerly an employee at the Department of Biochemistry at the Institute for Cancer Research. In the Authophagy article Bøe is first author.
The abstract from the "Blood" article:
Treatment of acute promyelocytic leukemia (APL) with all-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO) represents a paradigm in targeted cancer therapy as these drugs cause clinical remission by affecting the stability of the fusion oncoprotein promyelocytic leukemia (PML)/retinoic acid receptor alpha (RARA). Previous studies have implicated the ubiquitin-proteasome pathway as the main mechanism involved in therapy induced PML/RARA degradation. Here we have investigated a role of autophagy, a protein degradation pathway that involves proteolysis of intracellular material within lysosomes. We found that both ATRA and ATO induce autophagy via the mTOR pathway in APL cells and that autophagic degradation contributes significantly both to the basal turnover as well as the therapy induced proteolysis of PML/RARA. In addition, we observed a correlation between autophagy and therapy-induced differentiation of APL cells. Given the central role of the PML/RARA oncoprotein in APL pathogenesis, this study highlights an important role of autophagy in the development and treatment of this disease.
Article about the project from the Norwegian Cancer Society (in Norwegian): Celler spiser kreftfremkallende komponenter
A shorter version of the article at "forskning.no" - a national popular science web page: "Celler spiser kreften"
The theme is also covered in "Dagens Medisin" - a specialized newspaper for the sector of health published every fortnight: "Baner vei for ny behandling?"
Autophagy contributes to therapy-induced degradation of the PML/RARA oncoprotein.
Isakson P, Bjørås M, Bøe SO, Simonsen A.
Blood. 2010 Jun 23. [Epub ahead of print]
Autophagic degradation of an oncoprotein.
Bøe SO, Simonsen A.
Autophagy. 2010 Oct 19;6(7). [Epub ahead of print]