Institute seminar April 21 10.30

Andreas Brech

A. Brech
A. Brech

The institute seminar on Wednesday April 21st is given by Andreas Brech from the Department of Biochemistry.

Title of his talk: Autophagy in cancer


The seminar takes place in Seminar Rooms 1&2 (New Research Building Montebello) and starts at 10:30.

Abstract:

Autophagy is an evolutionary highly conserved process that mediates the removal/degradation of various intracellular substrates. The term macroautophagy describes the degradation of cytosolic content, which serves as source for cellular building blocks under metabolic stress condition. The normally low basal autophagic flux can also be rapidly increased upon other stimuli such as hypoxia, cytokines, hormones and DNA damage, indicating an important role for autophagy in maintaining cellular homeostasis. Alterations in this pathway have recently been linked to carcinogenesis. Accordingly many cancer types harbor mutations that localize to pro-autophagic genes such as LKB1, p53, Beclin 1, UVRAG and Bif-1, or have gain-of-function mutations in anti-autophagy genes such as Akt, Ras, Bcl-2 and PI3KC1.

We have been studying the function of several important mediators of the autophagic response, such as p62 and Alfy. Both proteins contain binding domains that are interacting with core components of the autophagic machinery. p62 targets ubiquitinated substrates and mediates autophagic sequestration/degradation through interaction with LC3, a key protein in the sequestration process. Various substrates such as damaged organelles, mitochondria, pathogens and protein aggregates are taken care of in this manner. However, p62 is also an important signal transduction adaptor and it has recently been shown that several signaling pathways, such as NF-kB regulation, are downregulated in cells overexpressing p62. Thus tumorigenesis could be promoted in autophagy-deficient cancer cell due to reduced p62 turnover through autophagy. Our aim is to better understand how the diverse functions of these adaptor proteins are integrated on the cellular level.

 

Links:

Home page of Andreas Brech's group - Unit of Cellular Electron Microscopy

Department of Biochemistry

Institute for Cancer Research

Institute seminars, spring 2010