-->PONE-D-26-09739-->-->Identification of CAND1 as a DNA-dependent protein kinase-regulated coactivator of androgen receptor and the ARv7 splice variant -->-->PLOS One

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S.L.G., K.R., and C.C. were partially supported by CPRIT grants RP200504 and RP210227, by NIH P30 shared resource grant CA125123, by NIEHS grants P30 ES030285 and P42 ES027725, and by NIH grants S10OD032185, U54CA274321, and R21DE032344.

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Additional Editor Comments:

The authors have addressed important issue of coregulator action of full length and variant androgen receptor. There are some minor suggestions for revision.

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Reviewers' comments:

Reviewer's Responses to Questions

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1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. -->

Reviewer #1: Yes

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-->2. Has the statistical analysis been performed appropriately and rigorously? -->

Reviewer #1: Yes

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Reviewer #1: Yes

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Reviewer #1: Yes

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-->5. Review Comments to the Author

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Reviewer #1: This is an elegant mechanistic study on novel co-factors of AR and ARv7 in prostate cancer. The experiments are well designed and conclusions are justified by the results.

Please see some minor points below:

Line 80, p4: please add more recent studies on AR interactome, using co-IP and MS. For example: PLoS One. 2024 Dec 13;19(12):e0309491. doi:10.1371/journal.pone.0309491. eCollection 2024.PMID: 39671399

Line 102 p5: typo (coactivator)

Line 132 p6: typo, profiling twice

Line 154 p7: where are the modifications highlighted? This should be clearly indicated.

Figure 1 A, bottom panel: it is not clear what the labels DMSO/Vehicle and DMSO/100nM R1881 refer too. This is not described in the main text either.

Lines 391-393, p16: The authors explain why they use NE from Hela which is essentially to pick a cell line without AR/ARv7 and a good source of RNA pol II machinery and CoRs. However, would the CoRs be less specific to prostate cancer than using a prostate cancer cell line without AR/ARv7, such as PC3 or DU154? This point should be at least discussed.

Figure 4 A: the scale for the bottom graphs is different from the top, which is understandable considering the amount of change. However, in the bottom panel changes are a fraction of those at the top. Is there any repercussion on the biological significance and interpretation of these results?

Figure 5B: Are the labels at the top correct? Should second lane be + ATP?

Line 719 p29: typo ‘TATA binding interacting protein’.

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Reviewer #1: No

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Identification of CAND1 as a DNA-dependent protein kinase-regulated coactivator of androgen receptor and the ARv7 splice variant

PONE-D-26-09739R1

Dear Dr. Foulds,

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Zoran Culig

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