CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-microtubule attachment.
Proper attachment of microtubules to kinetochores is essential for accurate chromosome segregation. Here, we report a novel protein involved in kinetochore-microtubule attachment, chromosome alignment-maintaining phosphoprotein (CAMP) (C13orf8, ZNF828). CAMP is a zinc-finger protein containing three characteristic repeat motifs termed the WK, SPE, and FPE motifs. CAMP localizes to chromosomes and the spindle including kinetochores, and undergoes CDK1-dependent phosphorylation at multiple sites during mitosis. CAMP-depleted cells showed severe chromosome misalignment, which was associated with the poor resistance of K-fibres to the tension exerted upon establishment of sister kinetochore bi-orientation. We found that the FPE region, which is responsible for spindle and kinetochore localization, is essential for proper chromosome alignment. The C-terminal region containing the zinc-finger domains negatively regulates chromosome alignment, and phosphorylation in the FPE region counteracts this regulation. Kinetochore localization of CENP-E and CENP-F was affected by CAMP depletion, and by expressing CAMP mutants that cannot functionally rescue CAMP depletion, placing CENP-E and CENP-F as downstream effectors of CAMP. These data suggest that CAMP is required for maintaining kinetochore-microtubule attachment during bi-orientation.
Institute of Development, Aging and Cancer, Tohoku University, Miyagi, Japan.
Go
G
Itoh
Shin-ichiro
S
Kanno
Kazuhiko S K
KS
Uchida
Shuhei
S
Chiba
Shiro
S
Sugino
Kana
K
Watanabe
Kensaku
K
Mizuno
Akira
A
Yasui
Toru
T
Hirota
Kozo
K
Tanaka
D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002877:Chromosomes, Human; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism* / Q000648:ultrastructure; D064246:Mad2 Proteins; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D008938:Mitosis; D010750:Phosphoproteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D034622:RNA Interference; D008941:Spindle Apparatus / Q000648:ultrastructure
C555812:CHAMP1 protein, human; D002868:Chromosomal Proteins, Non-Histone; C120552:MAD2L2 protein, human; D064246:Mad2 Proteins; D010750:Phosphoproteins; D011506:Proteins