VRK1/VRK2 phosphorylate BANF1

Stable Identifier
Homo sapiens
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In mitotic prophase, chromatin detaches from the nuclear envelope, and this contributes to the nuclear envelope breakdown. VRK1 (and possibly VRK2) mediated phosphorylation of BANF1 (BAF), a protein that simultaneously interacts with DNA, LEM-domain inner nuclear membrane proteins, and lamins (Zheng et al. 2000, Shumaker et al. 2001, Haraguchi et al. 2001, Mansharamani and Wilson 2005, Brachner et al. 2005) is considered to be one of the key steps in the detachment of the nuclear envelope from chromatin (Bengtsson and Wilson 2006, Nichols et al. 2006, Gorjanacz et al. 2007).

BANF1 (BAF i.e. barrier-to-autointegration factor) is a DNA-binding protein that was initially discovered as a regulator of retroviral integration (Lee and Craigie 1994, Lee and Craigie 1998). BANF1 (BAF) binds DNA non-specifically as a homodimer (Zheng et al. 2000). Proteins of the inner nuclear membrane that possess a LEM domain, TMPO (LAP2beta), EMD (emerin), LEMD3 (MAN1) and LEMD2 (LEM2), form three-way complexes with BANF1 and lamins - intermediary filaments of the nucleoplasm (Shumaker et al. 2001, Holaska et al. 2003, Mansharamani and Wilson 2005, Brachner et al. 2005). These complexes are thought to be important for the structure of the nuclear lamina and also enable attachment of chromatin to the nuclear envelope (Haraguchi et al. 2001, Dechat et al. 2004).

In mitosis, VRK1 (and to a lesser extent VRK2) serine/threonine kinase phosphorylates BANF1 (BAF) on serine residue S4 and threonine residues T2 and T3 (Nichols et al. 2006, Gorjanacz et al. 2007, Asencio et al. 2012). Only VRK2 isoform VRK2-2 which can localize to the nucleus (Blanco et al. 2006) is annotated as BANF1 kinase. Phosphorylated BANF1 (BAF) dissociates from chromatin and the inner nuclear membrane proteins (Bengtsson and Wilson 2006), allowing chromatin to detach from the nuclear envelope.

VRK1 and VRK2 are autophosphorylated but not all autophosphorylation sites have been mapped and the impact of autophosphorylation on catalytic activity has not been determined.

Literature References
PubMed ID Title Journal Year
12493765 Transcriptional repressor germ cell-less (GCL) and barrier to autointegration factor (BAF) compete for binding to emerin in vitro

Lee, KK, Kowalski, AK, Holaska, JM, Wilson, KL

J. Biol. Chem. 2003
11285238 LAP2 binds to BAF.DNA complexes: requirement for the LEM domain and modulation by variable regions

Wilson, KL, Craigie, R, Shumaker, DK, Lee, KK, Tanhehco, YC

EMBO J. 2001
16495336 The vaccinia-related kinases phosphorylate the N' terminus of BAF, regulating its interaction with DNA and its retention in the nucleus

Traktman, P, Wiebe, MS, Nichols, RJ

Mol. Biol. Cell 2006
16704422 The subcellular localization of vaccinia-related kinase-2 (VRK2) isoforms determines their different effect on p53 stability in tumour cell lines

Vega, FM, Klimcakova, L, Lazo, PA, Blanco, S

FEBS J. 2006
7937898 Protection of retroviral DNA from autointegration: involvement of a cellular factor

Lee, MS, Craigie, R

Proc Natl Acad Sci U S A 1994
22770216 Coordination of kinase and phosphatase activities by Lem4 enables nuclear envelope reassembly during mitosis

Wallenfang, MR, Mall, M, Davidson, IF, Santarella-Mellwig, R, Ly-Hartig, TB, Asencio, C, Gorjánácz, M, Mattaj, IW

Cell 2012
15681850 Direct binding of nuclear membrane protein MAN1 to emerin in vitro and two modes of binding to barrier-to-autointegration factor

Wilson, KL, Mansharamani, M

J. Biol. Chem. 2005
11792822 BAF is required for emerin assembly into the reforming nuclear envelope

Wilson, KL, Haraguchi, T, Hiraoka, Y, Yoneda, Y, Segura-Totten, M, Matsuoka, Y, Lee, KK, Koujin, T

J. Cell. Sci. 2001
16339967 LEM2 is a novel MAN1-related inner nuclear membrane protein associated with A-type lamins

Gotzmann, J, Foisner, R, Reipert, S, Brachner, A

J. Cell. Sci. 2005
10908652 Barrier-to-autointegration factor (BAF) bridges DNA in a discrete, higher-order nucleoprotein complex

Zheng, R, Ghirlando, R, Craigie, R, Krause, M, Lee, MS, Mizuuchi, K

Proc. Natl. Acad. Sci. U.S.A. 2000
9465049 A previously unidentified host protein protects retroviral DNA from autointegration

Lee, MS, Craigie, R

Proc Natl Acad Sci U S A 1998
17170708 Caenorhabditis elegans BAF-1 and its kinase VRK-1 participate directly in post-mitotic nuclear envelope assembly

Galy, V, López-Iglesias, C, Klerkx, EP, Askjaer, P, Santarella, R, Mattaj, IW, Gorjánácz, M

EMBO J. 2007
16371512 Barrier-to-autointegration factor phosphorylation on Ser-4 regulates emerin binding to lamin A in vitro and emerin localization in vivo

Wilson, KL, Bengtsson, L

Mol. Biol. Cell 2006
15546916 LAP2alpha and BAF transiently localize to telomeres and specific regions on chromatin during nuclear assembly

Korbei, B, Haraguchi, T, Dechat, T, Foisner, R, Furukawa, K, Daigle, N, Ellenberg, J, Gajewski, A, Gerlich, D

J. Cell. Sci. 2004
Catalyst Activity

protein serine/threonine kinase activity of VRK1/VRK2 [nucleoplasm]

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