KLP38B: A Mitotic Kinesin-related Protein That Binds PP1

Alphey, Luke; Parker, Louise; Hawcroft, Gillian; Guo, Yuan; Kaiser, Kim; Morgan, Gareth

doi:10.1083/jcb.138.2.395

Cited by 53 publications

(41 citation statements)

References 88 publications

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“…KIF14 could share this function: PSORT II (http://psort.ims.utokyo.ac.jp/form2.html) predicts 78.3% probability of nuclear localization for KIF14 (despite the absence of a nuclear localization signal). Post-translational regulation of KLP38B activity is suggested by its in vitro association with protein phosphatase type 1 (PP1) (Alphey et al, 1997), while nebbish expression is regulated by the pRb/E2F system (Dimova et al, 2003). The KIF14 promoter contains E2F consensus binding sequences conserved between mouse and human (as determined by ConSite analysis, http:// mordor.cgb.ki.se/cgi-bin/CONSITE/consite), suggesting that similar regulation might function in mammalian cells.…”

Section: Discussionmentioning

confidence: 99%

KIF14 is a candidate oncogene in the 1q minimal region of genomic gain in multiple cancers

et al. 2005

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Gain of chromosome 1q31-1q32 is seen in >50% of retinoblastoma and is common in other tumors. To define the minimal 1q region of gain, we determined genomic copy number by quantitative multiplex PCR of 14 sequence tagged sites (STSs) spanning 1q25.3-1q41. The most frequently gained STS at 1q32.1 (71%; 39 of 55 retinoblastoma) defined a 3.06 Mbp minimal region of gain between flanking markers, containing 14 genes. Of these, only KIF14, a putative chromokinesin, was overexpressed in various cancers by real-time RT-PCR. KIF14 mRNA was expressed in 20/22 retinoblastoma samples 100-1000-fold higher than in retina (t-test P ¼ 0.00002); cell lines (n ¼ 10) had higher levels than tumors (n ¼ 12) (P ¼ 0.009). KIF14 protein was overexpressed in retinoblastoma tumors and breast cancer cell lines by immunoblot. KIF14 was expressed in 4/4 breast cancer cell lines 31-92-fold higher than in normal breast tissue, in 5/5 medulloblastoma cell lines 22-79-fold higher than in fetal brain, and in 10/22 primary lung tumors 3-34-fold higher than in normal lung. Patients with lung tumors that overexpress KIF14 showed a trend toward decreased survival. KIF14 may thus be important in oncogenesis, and has promise as a prognostic indicator and therapeutic target.

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Section: Discussionmentioning

confidence: 99%

KIF14 is a candidate oncogene in the 1q minimal region of genomic gain in multiple cancers

et al. 2005

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“…In addition, although chromosome arms can bind MTs in these spindles (Fuge, 1990;LaFountain et al, 2001), they do not display the extensive oscillations observed in vertebrate mitotic cells (D. Zhang, personal communication), presumably owing to the lack of a polar ejection force (LaFountain et al, 2001). Likewise, extensive metaphase chromosome oscillations do not occur in early Drosophila embryonic and Xenopus egg extract spindles (Maddox et al, 2002;BrustMasher and Scholey, 2002;Maddox et al, 2003), even though chromokinesins are present and play an important role in aligning chromosomes at the metaphase plate (Alphey et al, 1997;Vernos et al, 1995;Antonio et al, 2000;Funabiki and Murray, 2000). The extremely fast flux rates in these spindles probably produce a sufficiently high tension at kinetochores that the switch to the depolymerization state is prevented (Maddox et al, 2003) (Table 1).…”

Section: Looking Back To See Forwardmentioning

confidence: 99%

Spindle microtubules in flux

Rogers

Sharp

2005

Journal of Cell Science

127

118

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Accurate and timely chromosome segregation is a task performed within meiotic and mitotic cells by a specialized force-generating structure – the spindle. This micromachine is constructed from numerous proteins, most notably the filamentous microtubules that form a structural framework for the spindle and also transmit forces through it. Poleward flux is an evolutionarily conserved mechanism used by spindle microtubules both to move chromosomes and to regulate spindle length. Recent studies have identified a microtubule-depolymerizing kinesin as a key force-generating component required for flux. On the basis of these findings, we propose a new model for flux powered by a microtubule-disassembly mechanism positioned at the spindle pole. In addition, we use the flux model to explain the results of spindle manipulation experiments to illustrate the importance of flux for proper chromosome positioning.

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“…4 This finding is consistent with the known functions of the Drosophila homolog of KIF14, Klp38B, which binds chromatin, acts as a microtubule-dependent molecular motor (like all kinesins) and is involved in formation of the mitotic spindle. [5][6][7][8] In a microarray study, KIF14 expression was found to be cell cycle regulated with peak expression in S phase 9 ; the KIF14 promoter is bound by E2F4 and p130. 10 In summary, these data suggest that KIF14 plays an important role in mitosis.…”

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confidence: 99%

KIF14 mRNA expression is a predictor of grade and outcome in breast cancer

Corson

Gallie

2006

Intl Journal of Cancer

105

103

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Gain of chromosome 1q is a hallmark of breast cancer, and likely reflects oncogene amplification. We previously identified mitotic kinesin KIF14 (kinesin family member 14) as an overexpressed candidate oncogene in the 1q31.3-1q32.1 minimal region of genomic gain in breast cancer cell lines. KIF14 also showed high expression in other cancers, notably an association with survival in lung tumors. We now report KIF14 expression in 99 primary breast tumors and 10 normal breast controls. Measured by realtime RT-PCR, KIF14 was overexpressed 10-fold on average in tumors relative to normals (t test p 5 0.000054); expression increased with grade (ANOVA p 5 0.000006). Infiltrating ductal carcinomas had higher KIF14 levels than lobular (p 5 0.017), and estrogen receptor (ER) negative tumors had higher KIF14 levels than ER positive tumors (t test p 5 0.030). KIF14 expression correlated positively with Ki-67 mRNA level (Spearman r 5 0.692, p 5 0.000001), fraction of positive nodes (r 5 0.227, p 5 0.024) and percent invasive cells (r 5 0.360, p 5 0.0002), and negatively with percent fatty stroma (r 5 20.258, p 5 0.010) and percent normal epithelium (r 5 20.291, p 5 0.003). KIF14 expression is thus tumor-specific and increased in more aggressive tumors. Indeed, KIF14 expression predicted overall survival (univariate Cox p 5 0.010), with an odds ratio of 3.60 (1.37-9.48), in 50 tumors with available outcome data. KIF14 overexpression also predicted decreased disease-free survival (log-rank p 5 0.049). These findings are the first evidence of association between expression of a mitotic kinesin and prognostic variables in breast cancer. ' 2006 Wiley-Liss, Inc.Key words: breast cancer; KIF14; kinesin; prognosis; real-time RT-PCR Recurrent chromosomal gains and losses are a feature of most cancers, and are presumed to reflect underlying oncogene amplification and tumor suppressor gene loss, respectively. In breast cancer, gain of 1q is the second-most common genomic gain (after 8q). Based on cumulative data in the Progenetix database of cytogenetic changes in cancer, 1 the minimal common region of genomic gain encompasses bands 1q31-1q32, gained or amplified in 44% of the 631 breast tumors in the database. 1 Gain of the long arm of chromosome 1 is one of the most frequent genomic aberrations in many tumor types, including retinoblastoma, strongly suggesting the presence of oncogene(s) in this region.Using quantitative multiplex PCR of genetic markers across the 1q31-1q32 region of chromosomal gain, we previously scanned DNA from 55 retinoblastoma and 12 breast cancer cell lines, and identified a 3.06 Mbp minimal region of gain. 2 Reverse transcription (RT)-PCR expression analyses of all genes in this region showed that only KIF14 (kinesin family member 14), a poorly characterized kinesin, was overexpressed 31-to 92-fold in 4 breast cancer cell lines compared with healthy breast tissue. Robust, cell line-specific protein expression, paralleling the mRNA level, was confirmed by immunoblot. KIF14 mRNA was also highly overexpressed in ...

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KLP38B: A Mitotic Kinesin-related Protein That Binds PP1

Cited by 53 publications

References 88 publications

KIF14 is a candidate oncogene in the 1q minimal region of genomic gain in multiple cancers

KIF14 is a candidate oncogene in the 1q minimal region of genomic gain in multiple cancers

Spindle microtubules in flux

KIF14 mRNA expression is a predictor of grade and outcome in breast cancer

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