PML Nuclear Bodies and SUMO in Cancer

Born in France, Anne Dejean-Assémat studied at the Université Pierre et Marie Curie in Paris, where she earned her PhD in 1983. Two years later she joined INSERM, the French National Institute for Health and Medical Research, and was appointed Research Director in 1991. Since 2003, she is the Director of the Laboratory of Nuclear Organization and Oncogenesis at the Pasteur Institute and of the INSERM Research Unit of Molecular and Cellular Biology of Tumors.

In 2004, she was elected to the French Academy of Sciences. Member of the European Molecular Biology Organization (EMBO), she is laureate of several international prizes (Hamdan Medicine Award 2000, Gagna & Van Heck 2003 and the L’Oréal-UNESCO Award for Women in Science 2010, for Europe).

A molecular biologist, Professor Anne Dejean has devoted her research to the molecular and cellular mechanisms involved in the development of human cancers. She discovered the role of mutations in retinoic acid receptors in liver cancer and promyelocytic leukemia and dissected the molecular mechanisms underlying their role in oncogenesis.

Her lab cloned the first retinoic acid receptor at an HBV integration site in a liver cancer, the PML-RARα  oncoprotein associated with promyelocytic leukemia and the PML tumor suppressor.

They discovered the RA-reversible disruption of PML Nuclear Bodies in leukemia and the role of sumoylation in the degradation of the PML-RARα oncoprotein and subnuclear organisation.

Anne Dejean and her collaborators have made important advances in the understanding of cancer and have opened up unique perspectives for the development of new treatment procedures.

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Anne Dejean discovered the role of mutations in retinoic acid receptors in liver cancer and promyelocytic leukemia and unveiled the molecular mechanisms underlying their role in oncogenesis. Her lab cloned the first retinoic acid receptor at an HBV integration site in a liver cancer, the PML-RARα  oncoprotein associated with promyelocytic leukemia and the PML tumor suppressor. She and her team have opened up unique perspectives for the development of new treatment procedures.

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FRONTAL: Among so many themes in the Biology field, what made you choose the Cancer one? Did you think this would be “the bet of your life”?

Anne Dejean-Assémat: I’ve always been interested in fundamental research and trying to understand the molecular and cellular mechanisms that can explain life. At first, I was much more interested in Basic Sciences and just pushed the boundaries of knowledge further, so this was my aim when I started as a researcher, but I progressively became interested in the disruption of the natural processes. And why? Well, because life is fantastic! I mean, the way all these molecules and these pathways work to make a full human being is fantastic. However, there is often disruption of these processes – and cancer, I think, is probably the pathology in which I would dare to say ALL processes are out of control. This way, cancer was a way of understanding the normal processes better. I also wanted to know more about the genetic defects responsible for human cancer, and at that point I began to develop an interest in treatments and their application to Medicine as well. These are the three most important stages of cancer study. I think it is very interesting for a basic researcher to focus on cancer, not only because of the underlying altered pathways, but also because of the impact of this disease, killing millions every year.

 F: And what about the retinoic acid? Where did your interest for this particular molecule come from?

ADA: Merely by pure chance! We were studying the role of the hepatitis B virus in the development of liver cancer, at a point in which the retinoic acids receptors were yet to be identified. Studying these patients with liver cancer helped us to acknowledge the role of this new gene. So I just wanted to know what this gene encoded for, and when we discovered that it was the receptor for the retinoic acid, I found it, of course, extremely interesting because this molecule is known to be involved in several pathways during human development. It is used in Medicine to treat acne and we realised it was also used to cure leukemia, so it was an exciting feeling of research.

F: What procedures and advances might possibly arise and be applied based on your discovery?

ADA: I think I would name two important implications. The first one is the notion of differentiation therapy – the idea is not to kill the malignant cell, like chemo, radio or conventional therapy do, but to put the leukemic cells in the right way, which is quite an innovative therapy. The second notion is directly related to our work: it is the oncogene-targeted anticancer therapy – you don’t treat all tumour cells without knowing which is their genetic defect, you just focus on the abnormal protein responsible for the disease, and target it. In our case we found that retinoic acid (and also nitroxide) were able to degrade the oncoprotein.

F: Do you consider your family to have played a major role in your growing process as a Woman and as a Scientist, helping therefore to build your image of Woman in Science, which earned you the L’Oréal Award?

ADA: Yes, I think family is important for any mother in any job. You find yourself involved in Science when you want to understand an observation, and I would say you fail in 98% of the cases. These are the moments (which is most of the time) when you really need a family and kids nearby. They make you feel capable of achieving what you want because they believe in a brighter future. And that is priceless.

F: How many lives can a woman have? How many roles can she play?

ADA: I think a woman, more than a man, plays many roles. However, Science is a full-time commitment. It is not something you quit from when you leave the lab – you carry it back home with you, it follows you everywhere. The same concept can be applied to children. They occupy 100% of your time. You are always between these two lives, so you need to be extremely organised and passionate about both of them.

Interviewers: Ana Luísa Pereira, Catarina Cardoso

Writers: Eva Alves