This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

4wzx

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 10:32, 25 December 2019

ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins

Structural highlights

4wzx is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	ULK3 (HUMAN)
Activity:	Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ULK3_HUMAN] Serine/threonine protein kinase that acts as a regulator of Sonic hedgehog (SHH) signaling and autophagy. Acts as a negative regulator of SHH signaling in the absence of SHH ligand: interacts with SUFU, thereby inactivating the protein kinase activity and preventing phosphorylation of GLI proteins (GLI1, GLI2 and/or GLI3). Positively regulates SHH signaling in the presence of SHH: dissociates from SUFU, autophosphorylates and mediates phosphorylation of GLI2, activating it and promoting its nuclear translocation. Phosphorylates in vitro GLI2, as well as GLI1 and GLI3, although less efficiently. Also acts as a regulator of autophagy: following cellular senescence, able to induce autophagy.^[1] ^[2] ^[3] [IST1_HUMAN] Proposed to be involved in specific functions of the ESCRT machinery. Is required for efficient abscission during cytokinesis, but not for HIV-1 budding. The involvement in the MVB pathway is not established. Involved in recruiting VPS4A and/or VPS4B to the midbody of dividing cells.^[4] ^[5]

Publication Abstract from PubMed

The Endosomal Sorting Complexes Required for Transport (ESCRT) machinery mediates the physical separation between daughter cells during cytokinetic abscission. This process is regulated by the abscission checkpoint, a genome protection mechanism that relies on Aurora B and the ESCRT-III subunit CHMP4C to delay abscission in response to chromosome missegregation. Here we show that Unc-51-like kinase 3 (ULK3) phosphorylates and binds ESCRT-III subunits via tandem MIT domains and thereby delays abscission in response to lagging chromosomes, nuclear pore defects and tension forces at the midbody. Our structural and biochemical studies reveal an unusually tight interaction between ULK3 and IST1, an ESCRT-III subunit required for abscission. We also demonstrate that IST1 phosphorylation by ULK3 is an essential signal required to sustain the abscission checkpoint and that ULK3 and CHMP4C are functionally linked components of the timer that controls abscission in multiple physiological situations.

ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins.,Caballe A, Wenzel DM, Agromayor M, Alam SL, Skalicky JJ, Kloc M, Carlton JG, Labrador L, Sundquist WI, Martin-Serrano J Elife. 2015 May 26;4. doi: 10.7554/eLife.06547. PMID:26011858^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Young AR, Narita M, Ferreira M, Kirschner K, Sadaie M, Darot JF, Tavare S, Arakawa S, Shimizu S, Watt FM, Narita M. Autophagy mediates the mitotic senescence transition. Genes Dev. 2009 Apr 1;23(7):798-803. doi: 10.1101/gad.519709. Epub 2009 Mar 11. PMID:19279323 doi:http://dx.doi.org/10.1101/gad.519709
↑ Maloverjan A, Piirsoo M, Michelson P, Kogerman P, Osterlund T. Identification of a novel serine/threonine kinase ULK3 as a positive regulator of Hedgehog pathway. Exp Cell Res. 2010 Feb 15;316(4):627-37. doi: 10.1016/j.yexcr.2009.10.018. Epub, 2009 Oct 21. PMID:19878745 doi:http://dx.doi.org/10.1016/j.yexcr.2009.10.018
↑ Maloverjan A, Piirsoo M, Kasak L, Peil L, Osterlund T, Kogerman P. Dual function of UNC-51-like kinase 3 (Ulk3) in the Sonic hedgehog signaling pathway. J Biol Chem. 2010 Sep 24;285(39):30079-90. doi: 10.1074/jbc.M110.133991. Epub, 2010 Jul 19. PMID:20643644 doi:http://dx.doi.org/10.1074/jbc.M110.133991
↑ Bajorek M, Morita E, Skalicky JJ, Morham SG, Babst M, Sundquist WI. Biochemical analyses of human IST1 and its function in cytokinesis. Mol Biol Cell. 2009 Mar;20(5):1360-73. doi: 10.1091/mbc.E08-05-0475. Epub 2009, Jan 7. PMID:19129479 doi:http://dx.doi.org/10.1091/mbc.E08-05-0475
↑ Agromayor M, Carlton JG, Phelan JP, Matthews DR, Carlin LM, Ameer-Beg S, Bowers K, Martin-Serrano J. Essential role of hIST1 in cytokinesis. Mol Biol Cell. 2009 Mar;20(5):1374-87. doi: 10.1091/mbc.E08-05-0474. Epub 2009, Jan 7. PMID:19129480 doi:http://dx.doi.org/10.1091/mbc.E08-05-0474
↑ Caballe A, Wenzel DM, Agromayor M, Alam SL, Skalicky JJ, Kloc M, Carlton JG, Labrador L, Sundquist WI, Martin-Serrano J. ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins. Elife. 2015 May 26;4. doi: 10.7554/eLife.06547. PMID:26011858 doi:http://dx.doi.org/10.7554/eLife.06547

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4wzx"

@@ Line 1: / Line 1: @@
 ==ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins==
-<StructureSection load='4wzx' size='340' side='right' caption='[[4wzx]], [[Resolution|resolution]] 1.39&Aring;' scene=''>
+<StructureSection load='4wzx' size='340' side='right'caption='[[4wzx]], [[Resolution|resolution]] 1.39&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4wzx]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WZX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WZX FirstGlance]. <br>
@@ Line 20: / Line 20: @@
 </div>
 <div class="pdbe-citations 4wzx" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
 == References ==
 <references/>
@@ Line 25: / Line 28: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Non-specific serine/threonine protein kinase]]
 [[Category: Agromayor, M]]

4wzx

From Proteopedia

Revision as of 10:32, 25 December 2019

ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox