PMID- 10087256
OWN - NLM
STAT- MEDLINE
DCOM- 19990614
LR  - 20190508
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 144
IP  - 6
DP  - 1999 Mar 22
TI  - A conserved biogenesis pathway for nucleoporins: proteolytic processing of a
      186-kilodalton precursor generates Nup98 and the novel nucleoporin, Nup96.
PG  - 1097-112
AB  - The mammalian nuclear pore complex (NPC) is comprised of approximately 50 unique 
      proteins, collectively known as nucleoporins. Through fractionation of rat liver 
      nuclei, we have isolated >30 potentially novel nucleoporins and have begun a
      systematic characterization of these proteins. Here, we present the
      characterization of Nup96, a novel nucleoporin with a predicted molecular mass of
      96 kD. Nup96 is generated through an unusual biogenesis pathway that involves
      synthesis of a 186-kD precursor protein. Proteolytic cleavage of the precursor
      yields two nucleoporins: Nup98, a previously characterized GLFG-repeat containing
      nucleoporin, and Nup96. Mutational and functional analyses demonstrate that both 
      the Nup98-Nup96 precursor and the previously characterized Nup98 (synthesized
      independently from an alternatively spliced mRNA) are proteolytically cleaved in 
      vivo. This biogenesis pathway for Nup98 and Nup96 is evolutionarily conserved, as
      the putative Saccharomyces cerevisiae homologues, N-Nup145p and C-Nup145p, are
      also produced through proteolytic cleavage of a precursor protein. Using
      immunoelectron microscopy, Nup96 was localized to the nucleoplasmic side of the
      NPC, at or near the nucleoplasmic basket. The correct targeting of both Nup96 and
      Nup98 to the nucleoplasmic side of the NPC was found to be dependent on
      proteolytic cleavage, suggesting that the cleavage process may regulate NPC
      assembly. Finally, by biochemical fractionation, a complex containing Nup96,
      Nup107, and at least two Sec13- related proteins was identified, revealing that a
      major sub-complex of the NPC is conserved between yeast and mammals.
FAU - Fontoura, B M
AU  - Fontoura BM
AD  - Laboratory of Cell Biology, Howard Hughes Medical Institute, The Rockefeller
      University, New York 10021, USA.
FAU - Blobel, G
AU  - Blobel G
FAU - Matunis, M J
AU  - Matunis MJ
LA  - eng
SI  - GENBANK/AF071076
SI  - GENBANK/AF071077
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (DNA, Complementary)
RN  - 0 (Membrane Proteins)
RN  - 0 (Nuclear Pore Complex Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Nup107 protein, rat)
RN  - 0 (Protein Precursors)
RN  - 0 (RNA, Messenger)
RN  - 0 (nuclear pore complex protein 96)
RN  - 0 (nuclear pore complex protein 98)
SB  - IM
MH  - Alternative Splicing
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Fractionation
MH  - Conserved Sequence
MH  - DNA, Complementary/genetics
MH  - In Vitro Techniques
MH  - Membrane Proteins/genetics/isolation & purification/*metabolism
MH  - Microscopy, Immunoelectron
MH  - Molecular Sequence Data
MH  - Nuclear Envelope/metabolism/ultrastructure
MH  - *Nuclear Pore Complex Proteins
MH  - Nuclear Proteins/genetics/isolation & purification/*metabolism
MH  - Protein Precursors/genetics/isolation & purification/metabolism
MH  - Protein Processing, Post-Translational
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Sequence Homology, Amino Acid
PMC - PMC2150585
EDAT- 1999/03/24 00:00
MHDA- 1999/03/24 00:01
CRDT- 1999/03/24 00:00
PHST- 1999/03/24 00:00 [pubmed]
PHST- 1999/03/24 00:01 [medline]
PHST- 1999/03/24 00:00 [entrez]
AID - 10.1083/jcb.144.6.1097 [doi]
PST - ppublish
SO  - J Cell Biol. 1999 Mar 22;144(6):1097-112. doi: 10.1083/jcb.144.6.1097.