Browsing by Author "Lin, C-C"

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Rapid analysis of protein tyrosine sulfation/desulfation
(2012-09-01)
Wang, C-C
;
Lin, C-C
;
Chen, B-H
;
Hung, S-K
;
Yang, Y-S
YB-1 disrupts mismatch repair complex formation, interferes with MutS alpha recruitment on mismatch and inhibits mismatch repair through interacting with PCNA
(2014-10-23)
Chang, Y-W
;
Mai, R-T
;
Fang, W-H
;
Lin, C-C
;
Chiu, C-C
Y-box binding protein-1 (YB-1) is highly expressed in tumors and it participates in various cellular processes. Previous studies indicated that YB-1 binds to mispaired DNA and interacts with several mismatch repair (MMR)-related factors. However, its role in the MMR system remains undefined. Here, we found that YB-1 represses mutS homolog 6 (MSH6)-containing MMR complex formation and reduces MutS alpha mismatch binding activity by disrupting interactions among MMR-related factors. In an effort to elucidate how YB-1 exerts this inhibitory effect, we have identified two functional proliferating cell nuclear antigen (PCNA)interacting protein (PIP)-boxes that mediate YB-1/PCNA interaction and locate within the C-terminal region of YB-1. This interaction is critical for the regulatory role of YB-1 in repressing MutSa mismatch binding activity, disrupting MutS alpha/PCNA/G/T heteroduplex ternary complex formation and inhibiting in vitro MMR activity. The differential regulation of 3\' and 5\' nick-directed MMR activity by YB-1 was also observed. Moreover, YB-1 overexpression is associated with the alteration of microsatellite pattern and the enhancement of N-methyl-N\'-nitro-N-nitrosoguanidine (MNNG)-induced and spontaneous mutations. Furthermore, upregulation of other PIP-box-containing proteins, such as myeloid cell leukemia-1 (Mcl-1) and inhibitor of growth protein 1b (ING1b), has no impact on MMR complex formation and mutation accumulation, thus revealing the significant effect of YB-1 on regulating the MMR system. In conclusion, our study suggests that YB-1 functions as a PCNA-interacting factor to exert its regulatory role on the MMR process and involves in the induction of genome instability, which may partially account for the oncogenic potential of YB-1.