title: PARP6, a mono(ADP-ribosyl) transferase and a negative regulator of cell             proliferation, is involved in colorectal cancer development.
abstract: Poly(ADP-ribose) polymerase (PARP) is an enzyme that mediates post-translational             modification of proteins. Seventeen known members of the PARP superfamily can             be grouped into three classes based on catalytic activity: (i) classical poly(ADP-ribose)             polymerases, (ii) mono(ADP‑ribosyl) transferases and (iii) catalytically inactive             members. PARP6 belongs to the mono(ADP-ribosyl) transferase class, and here we             have found that PARP6 is a negative regulator of cell proliferation. Forced expression             of PARP6 in HeLa cells induced growth suppression, but a PARP6 mutant with a C-terminal             deletion lacking the catalytic domain had no effect. The PARP6-expressing cells             accumulated in the S-phase, and the magnitude of S-phase accumulation was observed             to be greater in cells expressing a PARP6 mutant with an N-terminal deletion,             lacking a putative regulatory domain. Immunohistochemical analysis revealed that             PARP6 positivity was found at higher frequencies in colorectal cancer tissues             with well-differentiated histology compared to those with poorly differentiated             histology. Furthermore, PARP6 positivity negatively correlated with the Ki-67             proliferation index. Kaplan-Meier analysis showed that PARP6-positive colorectal             cancer had a good prognosis. Based on these results, we propose that PARP6 acts             as a tumor suppressor through its role in cell cycle control.
authors.affiliation: Department of Biophysics, Istanbul University, Istanbul 34303, Turkey.
authors.forename: Handan
authors.initials: H
authors.lastname: Tuncel
authors.forename: Shinji
authors.initials: S
authors.lastname: Tanaka
authors.forename: Shiro
authors.initials: S
authors.lastname: Oka
authors.forename: Shiro
authors.initials: S
authors.lastname: Nakai
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Fukutomi
authors.forename: Mayumi
authors.initials: M
authors.lastname: Okamoto
authors.forename: Takahide
authors.initials: T
authors.lastname: Ota
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kaneko
authors.forename: Masaaki
authors.initials: M
authors.lastname: Tatsuka
authors.forename: Fumio
authors.initials: F
authors.lastname: Shimamoto
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D016196:S Phase / Q000235:genetics; D016415:Sequence Alignment
chemical_list: D036002:ADP Ribose Transferases; C579799:PARP6 protein, human; D011065:Poly(ADP-ribose) Polymerases