ADVERTISEMENT
ADVERTISEMENT

Directing degradation

By Edyta Zielinska Directing degradation Serhiy Pankiv The paper: S. Pankiv et al., “p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy,” J Biol Chem , 282:24131–45, 2007. (Cited in 113 papers) The finding: Terje Johansen and his colleagues at the University of Tromsø, Norway, discovered the specific molecule involved in targeting cellular waste for d

Edyta Zielinska

Directing degradation

Serhiy Pankiv

The paper:

S. Pankiv et al., “p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy,” J Biol Chem , 282:24131–45, 2007. (Cited in 113 papers)

The finding:

Terje Johansen and his colleagues at the University of Tromsø, Norway, discovered the specific molecule involved in targeting cellular waste for destruction via large double-membrane vesicles called autophagosomes. They found that the protein p62 binds both the ubiquitin-tagged trash and the light chain 3 (LC3) protein on the outside of the autophagosomal membrane. “It was the first paper that showed how directed autophagy might work,” says Vladimir Kirkin of the Johann Wolfgang Goethe University in Frankfurt, Germany.

The bonus:

p62 is also crucial for another process key to cellular cleanup: the clumping together of misfolded proteins before they are engulfed by autophagosomes. Not only does it traffic the aggregate to the right place, “p62...

The follow-up:

The Hot Paper revealed the amino acid sequence of the p62–LC3 binding region. Johansen teamed up with Kirkin, then a postdoc, and used this motif to find another protein called NBR1, which can bind to p62 or function independently to shuttle material to the autophagosome ( Mol Cell , 33:505–16, 2009).

The connection:

Several researchers have implicated p62 and defective autophagy in the formation of various cancers. In June, the Cancer Institute of New Jersey’s Eileen White showed that blocking p62 accumulation kept cells healthy while p62 overexpression promoted tumorigenesis ( Cell , 137:1062–75, 2009).

Percentage of cells containing misfolded protein aggregates:
p62 present: 60%
p62 knocked down by RNAi: 10%

Interested in reading more?

Magaizne Cover

Become a Member of

Receive full access to digital editions of The Scientist, as well as TS Digest, feature stories, more than 35 years of archives, and much more!
Already a member?
ADVERTISEMENT