P15 (PC4,Sub1) mediates the effects of several distinct activators on transcription in vitro in mammals. Functional deletion analyses revealed a bipartite structure of p15 comprising an amino-terminal regulatory domain and a carboxy-terminal cryptic DNA-binding domain. The activity of p15 is controlled by protein kinases that target the regulatory domain. Structural and functional similarities, including sequence homology to domains essential for cofactor function, cofactor activity, promiscuity with respect to transcriptional activators, and interactions with components of the basal transcription machinery, relate this novel cellular cofactor to viral immediate-early transcriptional regulators (Kretzschmar et al., 1994). The protein has ssDNA binding activity, and has been shown to recruit to induced DNA damage sites (Mortusewicz et al., 2015).

p15 (PC4,Sub1) is involved not only in transcription, but also in DNA replication, damage repair, chromatin formation, and cell cycle regulation. It is involved in the initial steps of the response of mammalian cells to DNA damage, and may facilitate subsequent steps in DNA repair (Mortusewicz et al., 2008, 2015). PC4 played a role in the extremely early reaction of DNA damage by identifying single-stranded DNA damage, and could be recruited early to the DNA damage site, thus possibly initiating or promoting the subsequent steps of DNA damage and repair.  The increased expression of p15 in response to DNA damage has suggested that it may be useful as a potential radiation biodosimeter for early assessment of DNA damage (Ma et al., 2022).

In Arabidopsis the p15 gene has been named KELP and was originally found by Yeast-two-hybrid to interact with a protein named KIWI  and both are similar to p15 (Cormack et al., 1998). Later this same KELP protein was found to interact with the tomato mosaic tobamovirus movement protein (Matsushita et al., 2001, Sasaki et al., 2009). More recently the same gene was identified as Arabidopsis novel microgametophyte defective mutant 1 (AtNMDM1) (At5g09250) in a CRISPR based approach to identify genes that affect exine development in pollen (Mi et al., 2022). Plants defective in this gene exhibited reduced fertility-reduced transmission through male and female gametophytes and abnormal pollen intine development (Mi et al., 2022).

There are at least 3 KELP (p15,PC4,Sub1) homologs in the maize genome.

Last updated June 2023 by John Gray

References:

Kretzschmar M, Kaiser K, Lottspeich F, Meisterernst M. A novel mediator of class II gene transcription with homology to viral immediate-early transcriptional regulators. Cell. 1994 Aug 12;78(3):525-34. doi: 10.1016/0092-8674(94)90429-4. PMID: 8062392.

Mortusewicz O, Roth W, Li N, Cardoso MC, Meisterernst M, Leonhardt H. Recruitment of RNA polymerase II cofactor PC4 to DNA damage sites. J Cell Biol. 2008 Dec 1;183(5):769-76. doi: 10.1083/jcb.200808097. PMID: 19047459; PMCID: PMC2592824.

Mortusewicz O, Evers B, Helleday T. PC4 promotes genome stability and DNA repair through binding of ssDNA at DNA damage sites. Oncogene. 2016 Feb 11;35(6):761-70. doi: 10.1038/onc.2015.135. Epub 2015 May 11. PMID: 25961912.

Ma L, Gong Q, Liu G, Chen J, Wang Y, Luo P, Shi C. Positive Cofactor 4 as a Potential Radiation Biodosimeter for Early Assessment. Dose Response. 2022 Feb 23;20(1):15593258221081317. doi: 10.1177/15593258221081317. PMID: 35221823; PMCID: PMC8874181.

Cormack RS, Hahlbrock K, Somssich IE. Isolation of putative plant transcriptional coactivators using a modified two-hybrid system incorporating a GFP reporter gene. Plant J. 1998 Jun;14(6):685-92. doi: 10.1046/j.1365-313x.1998.00169.x. PMID: 9681033.

Sasaki N, Ogata T, Deguchi M, Nagai S, Tamai A, Meshi T, Kawakami S, Watanabe Y, Matsushita Y, Nyunoya H. Over-expression of putative transcriptional coactivator KELP interferes with Tomato mosaic virus cell-to-cell movement. Mol Plant Pathol. 2009 Mar;10(2):161-73. doi: 10.1111/j.1364-3703.2008.00517.x. PMID: 19236566; PMCID: PMC6640241.

Matsushita Y, Deguchi M, Youda M, Nishiguchi M, Nyunoya H. The tomato mosaic tobamovirus movement protein interacts with a putative transcriptional coactivator KELP. Mol Cells. 2001 Aug 31;12(1):57-66. PMID: 11561731.

Mi L, Mo A, Yang J, Liu H, Ren D, Chen W, Long H, Jiang N, Zhang T, Lu P. Arabidopsis Novel Microgametophyte Defective Mutant 1 Is Required for Pollen Viability via Influencing Intine Development in Arabidopsis. Front Plant Sci. 2022 Apr 12;13:814870. doi: 10.3389/fpls.2022.814870. PMID: 35498668; PMCID: PMC9039731.