This document summarizes two scientific studies. The first study discovered a molecular switch in the cell nucleus that controls whether a cell survives or dies during autophagy. The second study found that noncoding 5S rRNA protects the p53 tumor suppressor gene by redirecting ribosomal proteins to inhibit the Hdm2 enzyme and increase p53 levels, inducing cell death in conditions of abnormal cell growth. Both studies represent potential new targets for developing improved medical treatments.

1. Molecular Switch Controls the Destiny of Self-Eating
Cells
AND
Discovered the Role of Noncoding 5S rRNA in
Protecting the P53 Tumor Suppressor Gene
ANA MARÍA MONTÚFAR PANTOJA
UNIVERSIDAD PONTIFICIA BOLIVARIANA

4. INTRODUCTION
Since the "Human Genome Project",
molecular biology took a big potential and
became a science essential to all branches of
medicine, because it allows the study of the
entire human genetic information.
In these times, medicine has been shows its
importance, because this is necessary to the
advance of knowledge of the pathology of
human diseases, the diagnostic methods and
the development of new therapeutic
techniques.

5. FIRST NEW
Molecular Switch Controls the
Destiny of Self-Eating Cells
This study by scientists at Karolinska
Institutet in Sweden, University of
Michigan, and University of California
San Diego, USA.
The main objective was discover
whether autophagy can be affected by
events in the cell nucleus.

6. FIRST NEW
The autophagy is a process whereby
the cell consumes parts of itself,
sometimes to cleaning up abnormal
proteins to protect the cell and when
stressed by external circumstances.
However this process sometimes leads
to cell death, by which it needs a
control.

7. FIRST NEW
The researchers discovered a signal chain located in the
nucleus serves as a kind of molecular switch that
determines whether the cell dies or survives:
DNA in is packed around histone
proteins
On which different enzymes can
attach acetyl groups.
Histone modification (epigenetic
regulation)
Some enzymes add the acetyl groups and
other enzymes remove them.
Influence gene expression
without changing the DNA
sequence.

8. FIRST NEW
The research group found that the process of
acetylation of histone H4, reduces the expression of
genes related to autophagy.
If this specific histone modification was blocked, the
autophagic cells died.

9. FIRST NEW
In my opinion this news gives a very
important contribution to the study of the
autophagy process, therefore to the
investigation of the patology of different
disease.
The most important detail is the
epigenetic regulation, because it can
modify the histone without affecting the
DNA sequence. This makes the
investigation more makes it more
accurate and objective, and thus be the
first step of future techniques and studies.

10. SECOND NEW
Discovered the Role of
Noncoding 5S rRNA in
Protecting the P53 Tumor
Suppressor Gene
The study by Cancer Metabolism
group at the Bellvitge Biomedical
Research Institute (IDIBELL),
Catalan Oncology Institute (ICO) and
the Division of Hematology-Oncology
of the University of Cincinnati, led by
George Thomas

11. SECOND NEW
The protein synthesis in ribosomes, using
mRNA transduction, is necessary for cell
growth. If this growth is not controlled, the cell
can develop disorders such as cancer and
anemia.
In cases of extreme forms of aberrant cell
growth, the p53 is activated to to induce a cell
death program.
In normal conditions, p53 is maintained at low
levels to avoid damaging healthy cells. The
Hdm2 is the enzyme that degrades p53 to
maintained that levels.

12. SECOND NEW
Ribosomes are composed of two subunits termed 40S
and 60S. The formation of the 60S involves, L5, L11 and
5S rRNA.
Damage to ribosomes or
hyperactivated ribosome
biogenesis.
L5/L11/5S rRNA pre-ribosomal
complex is redirected from
nascent ribosomes to the binding
and inhibition of Hdm2
Rise p53
Cell death

13. SECOND NEW
• The Thomas team showed that L5 and
L11 regulate Hdm2 in a mutually
dependent manner and that 5S rRNA
that regulates Hdm2 is also a positive
effector of Hdm4, a negative regulator
of p53.
• Giulio Donati, the first author of these
studies, demontrated the existence of
the L5/L11/5S rRNA pre-ribosomal
complex and its role as a tumor
suppressor.

14. SECOND NEW
In my opinion the development
of the mentioned mechanism is
quite important in the search for
a treatment of cancer associated
with the ribosome biogenesis,
because is something new and it
can be a breakthrough in the
study of tumors.

15. MEDICAL UTILITY
First New
According to Dr Bertrand Joseph at Karolinska
Institutet's Department of Oncology-Pathology, who
headed the study, all they have to do is select a
disease model and test whether there's anything to be
influenced whit the new signal network. So, this
represents a potential way to develop a news
treatments to many diseases that involves the
autophagy in its patology, such us ancer, diabetes,
obesity, cardiovascular disease, chronic inflammations,
Alzheimer's and Parkinson's diseases, as well as in
physiological adaptation to exercise, the development
of the immune system and ageing.

16. MEDICAL UTILITY
This study took a very important step
in the research of autophagy process,
but still lacks many investigations to
clarify and explain the specific method
and epigenetic regulation to use and
modify the genes of expression of
autophagy and thus develop and
improve techniques for the treatment
of the diseases, because they have to
search the best way to block that
specific histone to influencing
autophagy, avoiding side effects.

17. MEDICAL UTILITY
Second New
The cancer is a disease that has had a
great impact on the world's population, and
its treatments are so invasive and
sometimes nonspecific, therefore when the
patients undergo these procedures are
conditioned to suffer negative changes in
their body, because the treatment destroys
the tumoral cells but also affects the benign
cells. Therefore the discovery published in
this new, present a other alternative based
on molecular biology, apparently better
than chemotherapy and radiation.

18. MEDICAL UTILITY
Many of tumors have mutations in p53
or overexpress Hdm2 or Hdm4, which
blocks the activity of p53. So the
researchers have to working in the link
between ribosome biogenesis and
cancer, starting on a way or technique
that activates Hdm2-p53 checkpoint to
destroy tumor cells.

19. BIBLIOGRAPHY
• Martínez S. Lina María. Biología Molecular, 5 ed.
Medellín, UPB, Facultad de Medicina
• Molecular Switch Controls the Destiny of Self-Eating
Cells
http://www.sciencedaily.com/releases/2013/07/13071713
2248.htm
• Discovered the Role of Noncoding 5S rRNA in Protecting
the P53 Tumor Suppressor Gene
http://www.sciencedaily.com/releases/2013/07/13070314
0521.htm