PMID- 22247549
OWN - NLM
STAT- MEDLINE
DCOM- 20120424
LR  - 20240214
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 287
IP  - 10
DP  - 2012 Mar 2
TI  - Ubiquitination of human leukocyte antigen (HLA)-DM by different 
      membrane-associated RING-CH (MARCH) protein family E3 ligases targets different 
      endocytic pathways.
PG  - 7256-64
LID - 10.1074/jbc.M111.305961 [doi]
AB  - HLA-DM plays an essential role in the peptide loading of classical class II 
      molecules and is present both at the cell surface and in late endosomal 
      peptide-loading compartments. Trafficking of DM within antigen-presenting cells 
      is complex and is, in part, controlled by a tyrosine-based targeting signal 
      present in the cytoplasmic tail of DMbeta. Here, we show that DM also undergoes 
      post-translational modification through ubiquitination of a single lysine residue 
      present in the cytoplasmic tail of the alpha chain, DMalpha. Ubiquitination of DM by 
      MARCH1 and MARCH9 induced loss of DM molecules from the cell surface by a 
      mechanism that cumulatively involved both direct attachment of ubiquitin chains 
      to DMalpha and a functional tyrosine-based signal on DMbeta. In contrast, MARCH8-induced 
      loss of surface DM was entirely dependent upon the tyrosine signal on DMbeta. In the 
      absence of this tyrosine residue, levels of DM remained unchanged irrespective of 
      whether DMalpha was ubiquitinated by MARCH8. The influence of MARCH8 was indirect and 
      may have resulted from modification of components of the endocytic machinery by 
      ubiquitination.
FAU - Jahnke, Martin
AU  - Jahnke M
AD  - Division of Immunology, Department of Pathology, University of Cambridge, 
      Cambridge CB2 1QP, United Kingdom.
FAU - Trowsdale, John
AU  - Trowsdale J
FAU - Kelly, Adrian P
AU  - Kelly AP
LA  - eng
GR  - G0901682/MRC_/Medical Research Council/United Kingdom
GR  - G9800943/MRC_/Medical Research Council/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120113
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (HLA-D Antigens)
RN  - 0 (HLA-DM antigens)
RN  - 0 (Protein Sorting Signals)
RN  - 0 (Ubiquitin)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
MH  - Endocytosis/*physiology
MH  - HEK293 Cells
MH  - HLA-D Antigens/genetics/*metabolism
MH  - Humans
MH  - Protein Sorting Signals/*physiology
MH  - Protein Structure, Secondary
MH  - Protein Transport/physiology
MH  - Ubiquitin/genetics/*metabolism
MH  - Ubiquitin-Protein Ligases/genetics/*metabolism
MH  - Ubiquitination/*physiology
PMC - PMC3293585
EDAT- 2012/01/17 06:00
MHDA- 2012/04/25 06:00
PMCR- 2012/01/13
CRDT- 2012/01/17 06:00
PHST- 2012/01/17 06:00 [entrez]
PHST- 2012/01/17 06:00 [pubmed]
PHST- 2012/04/25 06:00 [medline]
PHST- 2012/01/13 00:00 [pmc-release]
AID - S0021-9258(20)61041-9 [pii]
AID - M111.305961 [pii]
AID - 10.1074/jbc.M111.305961 [doi]
PST - ppublish
SO  - J Biol Chem. 2012 Mar 2;287(10):7256-64. doi: 10.1074/jbc.M111.305961. Epub 2012 
      Jan 13.