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

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.

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.

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.

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 histoneproteins

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.

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.

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.

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

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.

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 ribosomebiogenesis.

L5/L11/5S rRNA pre-ribosomal

complex is redirected from

nascent ribosomes to the binding

and inhibition of Hdm2

Rise p53

Cell death

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.

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.

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.

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.

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.

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.

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