PMID- 10500183
OWN - NLM
STAT- MEDLINE
DCOM- 19991021
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 20
DP  - 1999 Sep 28
TI  - Autoproteolysis in nucleoporin biogenesis.
PG  - 11370-5
AB  - We have molecularly characterized a proteolytic cleavage in conserved nuclear
      pore complex proteins. This cleavage, previously demonstrated to be essential for
      the biogenesis of two nuclear pore complex proteins in mammals (Nup98 and Nup96) 
      and yeast (Nup145-N and Nup145-C), occurs between Phe and Ser residues within a
      highly conserved domain in a polyprotein precursor. Here, we show that a protease
      is not involved in the cleavage event. By using a combination of domain mapping
      and site-directed mutagenesis, we demonstrate that the human nuclear pore complex
      protein Nup98 specifically cleaves itself between F863 and S864. A region of
      Nup98, amino acids 715-920, is able to cleave, whereas a smaller region, amino
      acids 772-920, does not cleave. In addition, we have generated a Nup98 mutant
      that cleaves under defined conditions in vitro. Further, the two cleaved
      fragments of Nup98 form a complex, providing a possible mechanism whereby
      specific, yet low-affinity, binding between Nup98 and Nup96 is responsible for
      the nuclear targeting of Nup96. Although apparently unrelated evolutionarily,
      Nup98 has converged on an autoproteolytic biogenesis mechanism similar to that of
      hedgehog proteins, the inteins, and the N-terminal nucleophile proteins.
FAU - Rosenblum, J S
AU  - Rosenblum JS
AD  - Laboratory of Cell Biology, Rockefeller University, New York, NY 10021, USA.
      rosenbj@rockvax.rockefeller.edu
FAU - Blobel, G
AU  - Blobel G
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Nuclear Proteins)
RN  - EC 3.4.- (Endopeptidases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Conserved Sequence
MH  - Endopeptidases/*physiology
MH  - Humans
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Nuclear Envelope/*chemistry
MH  - Nuclear Proteins/*metabolism
PMC - PMC18040
EDAT- 1999/09/29 00:00
MHDA- 1999/09/29 00:01
CRDT- 1999/09/29 00:00
PHST- 1999/09/29 00:00 [pubmed]
PHST- 1999/09/29 00:01 [medline]
PHST- 1999/09/29 00:00 [entrez]
AID - 10.1073/pnas.96.20.11370 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11370-5. doi:
      10.1073/pnas.96.20.11370.